Topic 3

Transmission of Stability Information Along a Two-stranded α-helical Coiled-Coil

Tropomyosin (Tm) is most widely known for its role in muscle contraction; its calcium-dependent cooperation with the troponin complex in regulating the interaction of myosin and actin required to generate the power stroke within the sarcomeres of muscle cells. Tm is expressed in all eukaryotic cell types in more than 40 isoforms that are widely distributed within individual cells. Consequently, Tm plays a critical role in numerous biologically relevant processes and is associated with several diseases, including cardiomyopathy and cancer.

Tm is a two-stranded α-helical coiled-coil of 284-residues per polypeptide chain. How signals are transmitted along this rod-like molecule of more than 400 Ao remains a major challenge for protein chemists. We made the first identification of a stability control region (SCR) residues 97-118 in the 284-residue tropomyosin sequence that controls overall protein stability but is not required for folding. We have shown that a single mutation L110A destabilizes the entire Tm (1-131) molecule, showing that the effect of this mutation is transmitted 165 Ao along the coiled-coil in the N-terminal direction. The single mutation A109L prevents the SCR from transmitting stabilizing information and separates the coiled-coil into two domains, one that is ~9oC more stable than wild type and one that is ~16oC less stable. Learning how stability information is transmitted along rod-like molecules is crucial to understanding function and signaling.

Selected publications are listed.

Kirwan, J.P. and R.S. Hodges. Transmission of stability information through the N-domain of tropomyosin is interrupted by a stabilizing mutation (A109L) in the hydrophobic core of the stability control region (97-118). J. Biol. Chem. 389: 4356-4366 (2014).

Kirwan, J.P. and R.S. Hodges. Critical interactions in the stability control region of tropomyosin. J. Structural Biology 170: 294-306 (2010). PMC2856757 PMID20144718

Hodges, R.S., J. Mills, S. McReynolds, J.P. Kirwan, B. Tripet, and D. Osguthorpe. Identification of a unique “stability control region” that controls protein stability of tropomyosin: a two-stranded a-helical coiled-coil. J. Mol. Biol. 392: 747-762 (2009). PMC2756485 PMID19627992

Kwok, S.C. and R.S. Hodges. Stabilizing and Destabilizing Clusters in the Hydrophobic Core of Long Two-stranded a-Helical Coiled-Coils. J. Biol. Chem. 279: 21576-21588 (2004).​

Publications

2015-2019

N/A

2010-2014

  1. Kirwan, J.P. and R.S. Hodges. Transmission of stability information through the N-domain of tropomyosin is interrupted by a stabilizing mutation (A109L) in the hydrophobic core of the stability control region (97-118). J. Biol. Chem. 389: 4356-4366 (2014).
  2. Kirwan, J.P. and R.S. Hodges. Critical interactions in the stability control region of tropomyosin. J. Structural Biology 170: 294-306 (2010).

2005-2009

  1. Schlegel, J., J.S. Redzic, C.C. Porter, V. Yurchenko, M. Bukrinsky, G.S. Armstrong, F. Zhang, N.G. Isern, J. DeGregori, R.S. Hodges and E.Z. Eisenmesser. Solution characterization of the extracellular region of CD147 and its interaction with its enzyme ligand cyclophilin A. J. Mol. Biol. 391: 518-535 (2009).
  2. Hodges, R.S., J. Mills, S. McReynolds, J.P. Kirwan, B. Tripet, and D. Osguthorpe. Identification of a unique “stability control region” that controls protein stability of tropomyosin: a two-stranded a-helical coiled-coil. J. Mol. Biol. 392: 747-762 (2009).
  3. Tsatskis, Y., S.C. Kwok, E. Becker, C. Gill, M. Smith, R.A.B. Keates, R.S. Hodges and J.M. Wood. Core residue replacements cause coiled-coil orientation switching in vitro and in vivo: Structure-function correlations for osmosensory transporter ProP. Biochemistry 47: 60-72 (2008).
  4. Smith, M.N., S.C. Kwok, R.S. Hodges and J.M. Wood. Structural and Functional Analysis of Pro Q: An osmoregulatory protein of Escherichia coli. Biochemistry 46: 3084-3095 (2007).
  5. Wardell, S.E., S.C. Kwok, L. Sherman, R.S. Hodges, and D.P. Edwards. Regulation of the amino-terminal transcription activation domain of progesterone receptor by a cofactor-induced protein folding mechanism. Molecular Cellular Biology 25: 8792-8808 (2005).
  6. Rashid, D.J., J. Bononi, B. Tripet, R.S. Hodges and D.W. Pierce. Monomeric and dimeric states exhibited by the kinesin-related motor protein KIFIA. J. Peptide Research 65: 538-549 (2005).
  7. Chana, M., B. Tripet, C.T. Mant and R.S. Hodges. Stability and specificity of heterodimer formation for the coiled-coil neck regions of the motor proteins Kif3A and Kif3B: The role of unstructured oppositely charged regions. J. Peptide Research 65: 209-220 (2005).

2000-2004

  1. Martin, S.L., M. Cruceanu, D. Branciforte, P. W.-L Li, S.C. Kwok, R.S. Hodges and M.C. Williams. Line-1 Retrotransposition requires the nucleic acid chaperone activity of ORF1 Protein. J. Mol. Biol. 348, 549-561 (2005).
  2. Lindhout, D.A., J.R. Litowski, P. Mercier, R.S. Hodges and B.D. Sykes. NMR solution structure of a highly stable de novo heterodimeric coiled-coil. Peptide Science (Biopolymers) 75: 367-375 (2004).
  3. Kwok, S.C. and R.S. Hodges. Effect of chain length on coiled-coil stability: decreasing stability with increasing chain length. Biopolymers (Peptide Science) 76: 378-390 (2004).
  4. Kwok, S.C. and R.S. Hodges. Stabilizing and Destabilizing Clusters in the Hydrophobic Core of Long Two-stranded a-Helical Coiled-Coils. J. Biol. Chem. 279: 21576-21588 (2004).
  5. Lu, S.M. and R.S. Hodges. Defining the minimum size of a hydrophobic cluster in two-stranded a-helical coiled-coils: effects on protein stability. Protein Science 13: 714-726 (2004).
  6. Hillar, A., B. Tripet, D.L. Zoetewey, J.M. Wood, R.S. Hodges and J.M. Boggs. Detection of a-helical coiled-coil dimer formation by spin-labeled synthetic peptides: A model parallel coiled-coil peptide and the antiparallel coiled-coil formed by a replica of the ProP C-terminus. Biochemistry42:15170-15178 (2003).
  7. Zoetewey, D.L., B. Tripet, T. Kutateladze, M. Overduin, J.M. Wood and R.S. Hodges. NMR solution structure of the cytoplasmic antiparallel coiled-coil domain from Escherichia coli ProP. J. Mol. Biol. 334:1063-1076 (2003).
  8. Kwok, S.C. and R.S. Hodges. Clustering of large hydrophobes in the hydrophobic core of two-stranded coiled-coils controls protein folding and stability. J. Biol. Chem. 278: 35248-35254 (2003).
  9. Lee, D.L., S. Ivaninskii, P. Burkhard and R.S. Hodges. Unique stabilizing interactions identified in the two-stranded a-helical coiled-coils: Crystal structure of a cortexillin I/GCN4 hybrid coiled-coil peptide. Protein Sci. 12: 1395-1405 (2003).
  10. De Crescenzo, G., J.R. Litowski, R.S. Hodges and M.D. O’Connor-McCourt. Real-time monitoring of the interactions of de novo designed coiled-coils using Surface Plasmon Resonance: Effect of chain length on the kinetic and thermodynamic constants of interaction. Biochemistry 42: 1254-1263 (2003).
  11. Mant, C.T. and R.S. Hodges. Design, synthesis and characterization of a-helices and coiled-coils. In: Synthesis of Peptides and Peptidomimetics. Houben-Weyl Methods of Organic Chemistry (M. Goodman, A. Felix, L. Moroder and C. Toniolo, Eds.) Thieme Stuttgart, Vol. E22d: 68-113 (2003).
  12. Litowski, J.R. and R.S. Hodges. Designing heterodimeric two-stranded a-helical coiled-coils: The effects of hydrophobicity and a-helical propensity on protein folding, stability, and specificity. J. Biol. Chem. 277: 37272-37279 (2002).
  13. Tripet, B. and R.S. Hodges. Helix Capping Interactions Stabilize the N-terminus of the Kinesin Neck Coiled-coil. J. Structural Biology 137: 220-235 (2002).
  14. Chana, M., C.T. Mant, B. Tripet and R.S. Hodges. The role of unstructured highly charged regions on the stability and specificity of dimerization of two-stranded a-helical coiled-coils: Neck region of kinesin-like motor protein Kif3A. J. Structural Biology 137: 206-219 (2002).
  15. Chen, Y., C.T. Mant and R.S. Hodges. Determination of stereochemistry stability coefficients of amino acid side-chains in an amphipathic a-helix. J. Peptide Research 59: 18-33 (2002).
  16. Ho, C.-Y., M.E. Houston, J.G. Adamson, R.S. Hodges and M. Smith. A possible mechanism for partitioning between homo- and hetero-dimerization of the yeast homeodomain proteins Mat a1 and Mat a2. J. Peptide Res 59: 34-43 (2002).
  17. Kwok. S.C., C.T. Mant and R.S. Hodges. Importance of Secondary Structural Specificity Determinants in Protein Folding: Insertion of a native b-sheet sequence into an a-helical coiled-coil. Protein Science 11: 1519-1531 (2002).
  18. Litowski, J.R. and R.S. Hodges. Designing heterodimeric two-stranded a-helical coiled-coils: The effect of chain length on protein folding, stability and specificity. J. Peptide Res. 58: 477-492 (2001).
  19. Baardsnes, J., M. Jelokhani-Niaraki, L.H. Kondejewski, M.J. Kuiper, C.M. Kay, R.S. Hodges and P.L. Davies. Antifreeze protein from Shorthorn Sculpin: Identification of the ice-binding surface. Protein Science 10: 2566-2576 (2001).
  20. Yu, B.Y., P.L. Privalov and R.S. Hodges. Contribution of translational and rotational motions to molecular association and aqueous solution. Biophys. J. 81: 1632-1642 (2001).
  21. Lee, D.L., P. Lavigne and R.S. Hodges. Are trigger sequences essential in the folding of two-stranded a-helical coiled-coils? J. Mol. Biol. 306: 539-553 (2001).
  22. Tripet, B., K. Wagschal, P. Lavigne, C.T. Mant and R.S. Hodges. Effects of side-chain characteristics on the stability and oligomerization state of a de novo designed model coiled-coil: Twenty amino acid substitutions in position "d". J. Mol. Biol. 300: 377-402 (2000).
  23. Yu, B.Y., K.C. Wagschal, C.T. Mant and R.S. Hodges. Trapping the Monomeric a-Helical State During Unfolding of Coiled-Coils by Reversed-Phase Chromatography. J. Chromatogr. A. 890: 81-94 (2000).
  24. Culham, D.E., B. Tripet, K.I. Racher, Voegele, R.T., R.S. Hodges and J.M. Wood. The role of carboxyl terminal a-helical coiled-coil domain in osmosensing by transporter ProP of Escherichia coli. J. Mol. Recognit.13: 309-322 (2000).

1995-1999

  1. Baardsnes, J., L.H. Kondejewski, R.S. Hodges, H. Chao, C.M. Kay and P.L. Davies. New ice-binding face for Type 1 antifreeze protein. FEBS Letters 463: 87-91 (1999).
  2. Yu, B.Y., P. Lavigne, P.L. Privalov and R.S. Hodges. A measure of disorder in a folded protein and its contribution to stability. J. Am. Chem. Soc. 121: 8443-8449 (1999).
  3. Wagschal, K., B. Tripet, P. Lavigne, C.T. Mant and R.S. Hodges. The role of position "a" in determining the stability and oligomerization state of a-helical coiled-coils: 20 amino acid stability coefficients in the hydrophobic core of proteins. Protein Sci. 8: 2312-2329 (1999).
  4. Loewen, M.C., H. Chao, M.E. Houston, J. Baardsnes, R.S. Hodges, C.M. Kay, B.D. Sykes, F.D. Sonnichsen and P.L. Davis. Alternative roles for putative ice binding residues in Type 1 Antifreeze protein. Biochemistry 38: 4743-4749 (1999).
  5. Yu, B.Y., P. Lavigne, C.M. Kay, R.S. Hodges and P.L. Privalov. Contribution of translational and rotational entropy to the unfolding of a dimeric coiled-coil. J. Physical Chemistry B 103: 2270-2278 (1999).
  6. Okamoto, P.M., B. Tripet, J. Litowski, R.S. Hodges and R.B. Vallee. Multiple coiled-coils are involved in dyamin self-assembly. J. Biol. Chem. 274: 10277-10286 (1999).
  7. Wagschal, K., B. Tripet and R.S. Hodges. De novo design of a model peptide sequence to examine the effects of single amino acid substitutions in the hydrophobic core on both stability and oligomerization state of coiled-coils. J. Mol. Biol. 285: 785-803 (1999).
  8. Kohn, W.D., C.M. Kay and R.S. Hodges. Orientation, positional additivity and oligomerization state effects of interhelical ion-pairs in a-helical coiled-coils. J. Mol. Biol. 283: 993-1012 (1998).
  9. Kohn, W.D. and R.S. Hodges. De novo design of a-helical coiled-coils and bundles: Protein models for development of design principles. Trends in Biotechnology 16: 379-389 (1998).
  10. Lavigne, P., M.P. Crump, S.M. Gagne, R.S. Hodges, C.M. Kay and B.D. Sykes. Insights into the Mechanism of heterodimerization from the 1H-NMR solution structure of the c-MYC-MAX heterodimeric leucine zipper. J. Mol. Biol. 281: 165-181 (1998).
  11. Kwok, S.C., B. Tripet, J.H. Man, M. Chana, P. Lavigne, C.T. Mant and R.S. Hodges. Structural cassette mutagenesis in a de novo designed protein: Proof of a novel concept for examining protein folding and stability. Biopolymers (Peptide Science) 47:101-123 (1998).
  12. Kohn, W.D., C.M. Kay and R.S. Hodges. Effects of Lanthanide binding on the stability of de novodesigned a-helical coiled-coils. J. Peptide Research 51: 9-18 (1998).
  13. Houston, M.E., H. Chao, R.S. Hodges, B.D. Sykes, C.M. Kay, F.D. Sönnichsen, M.C. Loewen and P.L. Davies. Binding of an oligopeptide to a specific plane of ice. J. Biol. Chem. 273: 11714-11718 (1998).
  14. Kohn, W.D., C.M. Kay, B.D. Sykes and R.S. Hodges. Metal ion-induced folding of a de novodesigned coiled-coil peptide. J. Am. Chem. Soc. 120: 1124-1132 (1998).
  15. Chao, H., D.L. Bautista, J. Litowski, R.T. Irvin and R.S. Hodges. The use of a heterodimeric coiled-coil system for biosensor application and affinity purification. J. Chromatography B 715: 307-329 (1998).
  16. Chao, H., M.E. Houston, R.S. Hodges, C.M. Kay, B.D. Sykes, M.C. Loewen, P.L. Davies and F.D. Sönnichsen. A diminished role for hydrogen bonds in antifreeze protein binding to ice. Biochemistry 36: 14652-14660 (1997).
  17. De Crovy-Chanel, A., R.S. Hodges, M. Kohiyama and G. Richarme. DNAJ potentiates the interaction of DNAK with a-helical peptides. BBRC 233: 627-630 (1997).
  18. Kohn, W.D., C.M. Kay and R.S. Hodges. Salt effects on the protein stability: Two-stranded a-helical coiled-coils containing inter- or intrahelical ion-pairs. J. Mol. Biol. 267: 1039-1052 (1997).
  19. Tripet, B., R.D. Vale and R.S. Hodges. Demonstration of coiled-coil interactions within the kinesin neck region using synthetic peptides: Implications for motor activity. J. Biol. Chem. 272: 8946-8956 (1997).
  20. Wallace, A., E. Bianchi, M.E. Houston, R.S. Hodges and A. Pessi. Topographical mimics of a structured peptide selected from a conformationally-homogeneous peptide combinatorial library. In: Innovations and Perspectives in Solid-Phase Synthesis (R. Epton, Ed.), pp. 553-556, Escom Scientific Publications, Leiden, The Netherlands (1997).
  21. Lavigne, P., M.P. Crump, S.M. Gagné, B.D. Sykes, R.S. Hodges and C.M. Kay. 1H-NMR Evidence for Two Buried Asn Side-Chains in the c-Myc-Max Heterodimeric a-Helical Coiled-coil. In:Techniques in Protein Chemistry VIII (D.R. Marshak, Ed.) Academic Press Inc. pp. 617-624 (1997).
  22. Kohn, W.D., C.T. Mant and R.S. Hodges. a-Helical protein assembly motifs. J. Biol. Chem. 272: 2583-2586 (1997).
  23. Kohn, W.D., C.M. Kay and R.S. Hodges. Positional dependence of the effects of negatively charged Glu side-chains on the stability of two-stranded a-helical coiled-coils. J. Peptide Sci. 3: 209-223 (1997).
  24. Chao, H., M.E. Houston, S. Grothe, C.M. Kay, M. O'Connor-McCourt, R.T. Irvin and R.S. Hodges. Kinetic study on the formation of a de novo designed heterodimeric coiled-coil: Use of surface plasmon resonance to monitor the association and dissociation of polypeptide chains. Biochemistry 35: 12175-12185 (1996).
  25. Houston, M.E., P. Campbell, B. Lix, C.M. Kay, B.D. Sykes and R.S. Hodges. Lactam bridge stabilization of a-helices: The role of hydrophobicity in controlling dimeric versus monomeric a-helices. Biochemistry 35: 10041-10050 (1996).
  26. Court, D.A., F.E. Nargang, H. Steiner, R.S. Hodges, W. Neupert and R. Lill. Role of the intermembrane space domain of the preprotein receptor Tom 22 in protein import into mitochondria. Molecular and Cellular Biology 16: 4035-4042 (1996).
  27. Chao, H., R.S. Hodges, C.M. Kay, S.Y. Gauthier and P.L. Davies. A natural variant of type I antifreeze protein with four ice-binding repeats is a particularly potent antifreeze. Protein Science 5: 1150-1156 (1996).
  28. Rothemund, S.E., E. Krause, M. Beyermann, M. Dathe, M. Bienert, R.S. Hodges, B.D. Sykes, F.D. Sönnichsen. Peptide destabilization by D-amino acids in single-stranded amphipathic a-helices. Peptide Research 9: 79-87 (1996).
  29. Tripet, B., L. Yu, D. Bautista, W.Y. Wong, R.T. Irvin and R.S. Hodges. Engineering a de novodesigned coiled-coil dimerization domain for rapid detection, purification and characterization of recombinant peptides and proteins. Protein Engineering 9: 1029-1042 (1996).
  30. Houston, M.E., A. Wallace, E. Bianchi, A. Pessi and R.S. Hodges. Use of conformationally restricted secondary structural element to display peptide libraries: A two-stranded a-helical coiled-coil stabilized by lactam bridges. J. Mol. Biol. 262: 270-282 (1996).
  31. Yu, B.Y., O.D. Monera, R.S. Hodges and P.L. Privalov. Investigation of electrostatic interactions in two-stranded coiled-coils through residue shuffling. Biophysical Chemistry 59: 299-314 (1996).
  32. Monera, O.D., F.D. Sonnichsen, L. Hicks, C.M. Kay and R.S. Hodges. The relative positions of alanine residues in the hydrophobic core control the formation of two-stranded or four-stranded a-helical coiled-coils. Protein Engineering 9: 353-363 (1996).
  33. Hodges, R.S. De novo design of a-helical proteins: Basic research to medical applications. Can. Soc. Biochemistry and Mol. Biol. Boehringer Mannheim Award Lecture. Biochem. Cell Biology 74: 133-154 (1996).
  34. Monera, O.D., N.E. Zhou, P. Lavigne, C.M. Kay and R.S. Hodges. Formation of parallel and antiparallel coiled-coils controlled by the relative positions of alanine residues in the hydrophobic core. J. Biol. Chem. 271: 3995-4001 (1996).
  35. Yu, B.Y., O.D. Monera, R.S. Hodges and P.L. Privalov. Ion-pairs significantly stabilize coiled-coils in the absence of electrolyte. J. Mol. Biol. 255: 367-372 (1996).
  36. Lavigne, P., F.D. Sönnichsen, C.M. Kay and R.S. Hodges. Interhelical salt-bridges, coiled-coil stability and specificity of dimerization. Science 271: 1136-1138 (1996).
  37. Rothemund, S., M. Beyerman, E. Krause, G. Krause, M. Bienert, R.S. Hodges, B.D. Sykes and F.D. Sönnichsen. Structure effects of double D-amino acid replacements: A NMR and CD study using amphipathic model helices. Biochemistry 34: 12954-12962 (1995).
  38. Kohn, W.D., O.D. Monera, C.M. Kay and R.S. Hodges. The effects of interhelical electrostatic repulsions between glutamic acid residues in controlling the dimerization and stability of two-stranded a-helical coiled-coils. J. Biol. Chem. 270: 25495-25506 (1995).
  39. Lavigne, P., L.H. Kondejewski, M.E. Houston, F.D. Sönnichsen, B. Lix, B.D. Sykes, R.S. Hodges and C.M. Kay. Preferential heterodimeric parallel coiled-coil formation by synthetic Max and C-Myc leucine zippers: A description of putative electrostatic interactions responsible for the specificity of interaction. J. Mol. Biol. 254: 505-520 (1995).
  40. Monera, O.D., T.J. Sereda, N.E. Zhou, C.M. Kay and R.S. Hodges. Relationship of side-chain hydrophobicity and a-helical propensity on the stability of the single-stranded amphipathic a-helix. J. of Peptide Science 1: 319-329 (1995).
  41. Houston, M.E., C.L. Gannon, C.M. Kay and R.S. Hodges. Lactam bridge stabilization of a-helical peptides: Ring size, orientation, and positional effects. J. Peptide Science 1: 274-282 (1995).
  42. Kohn, W.D., C.M. Kay and R.S. Hodges. Protein destabilization by electrostatic repulsions in the two-stranded a-helical coiled-coil/leucine zipper. Protein Science 4: 237-250 (1995).

1990-1994

  1. Su, J.Y., R.S. Hodges and C.M. Kay. Effect of chain length on the formation and stability of synthetic a-helical coiled-coils. Biochemistry 33: 15501-15510 (1994).
  2. Zhou, N.E., C.M. Kay and R.S. Hodges. The net energetic contribution of interhelical electrostatic attractions to coil-coil stability. Protein Engineering 7: 1365-1372 (1994).
  3. Monera, O.D., C.M. Kay and R.S. Hodges. Protein denaturation with guanidine hydrochloride or urea provides a different estimate of stability depending on the contributions of electrostatic interactions. Protein Science 3: 1984-1991 (1994).
  4. Zhou, N.E., O.D. Monera, C.M. Kay and R.S. Hodges. a-Helical propensities of amino acids in the hydrophobic face of an amphipathic a-helix. Protein and Peptide Letters 1: 114-119, 1994.
  5. Ho, C.-Y., J.G. Adamson, R.S. Hodges and M. Smith. Heterodimerization of the yeast Mat a1 and Mat a2 proteins is mediated by two leucine zipper like coiled-coil motifs. The EMBO Journal 13: 1403-1413 (1994).
  6. Monera, O.D., C.M. Kay and R.S. Hodges. Electrostatic interactions control the parallel and antiparallel orientation of a-helical chains in two-stranded a-helical coiled-coils. Biochemistry 33: 3862-3871 (1994).
  7. Zhou, N.E., C.M. Kay and R.S. Hodges. The role of interhelical ionic interactions in controlling protein folding and stability: De novo designed synthetic two-stranded a-helical coiled-coils. J. Molecular Biology 237: 500-512 (1994).
  8. Adamson, J.G., N.E. Zhou and R.S. Hodges. Structure, function and application of the coiled-coil protein folding motif. Current Opinion in Biotechnology 4: 428-437 (1993).
  9. Mant, C.T., N.E. Zhou and R.S. Hodges. The role of amphipathic helices in stabilizing peptide and protein structure. The Amphipathic Helix (R.M. Epand, Ed.), CRC Press Inc. pp. 39-64 (1993).
  10. Monera, O.D., N.E. Zhou, C.M. Kay and R.S. Hodges. Comparison of antiparallel and parallel two-stranded a-helical coiled-coils: Design, synthesis and characterization. J. Biol. Chem. 268: 19218-19227 (1993).
  11. Zhu, B.-Y., N.E. Zhou, C.M. Kay and R.S. Hodges. Packing and hydrophobicity effects on protein folding and stability. Effects of ß-branched amino acids, valine and isoleucine, on the formation and stability of two-stranded a-helical coiled-coils/leucine zippers. Protein Science 2: 383-394 (1993).
  12. Zhou, N.E., C.M. Kay, B.D. Sykes and R.S. Hodges. A single-stranded amphipathic a-helix in aqueous solution: Design, structural characterization and its application for determining a-helical propensities of amino acids. Biochemistry 32: 6190-6197 (1993).
  13. Zhou, N.E., C. M. Kay and R.S. Hodges. Disulfide bond contribution to protein stability: Positional effects of substitution in the hydrophobic core of the two-stranded a-helical coiled-coil. Biochemistry 32: 3178-3187 (1993).
  14. Zhu, B.-Y., N.E. Zhou, P.D. Semchuk, C.M. Kay and R.S. Hodges. Design, synthesis and structural characterization of model heterodimeric coiled-coil proteins. Int. J. Pept. Pro. Res. 40: 171-179 (1992).
  15. Zhou, N.E., C.M. Kay and R.S. Hodges. Synthetic model proteins: The relative contribution of leucine residues at the non-equivalent positions of the 3-4 hydrophobic repeat to the stability of the two-stranded a-helical coiled-coil. Biochemistry 31: 5739-5746 (1992).
  16. Zhou, N.E., B.-Y. Zhu, B.D. Sykes and R.S. Hodges. The relationship between amide proton chemical shifts and hydrogen bonding in amphipathic a-helical peptides. J. Am. Chem. Soc. 114: 4320-4326 (1992).
  17. Zhou, N.E., B.-Y. Zhu, C.M. Kay and R.S. Hodges. The two-stranded a-helical coiled-coil is an ideal model for studying protein stability and subunit interactions. Biopolymers 32: 419-426 (1992).
  18. Hodges, R.S. Unzipping the secrets of coiled-coils. Current Biology 2: 122-124 (1992).
  19. Zhou, N.E., C.M. Kay and R.S. Hodges. Synthetic model proteins: Positional effects of interchain hydrophobic interactions on stability of two-stranded a-helical coiled-coils. J. Biol. Chem. 267:2664-2670 (1992).
  20. Hodges, R.S., N.E. Zhou, C.M. Kay and P.D. Semchuk. Synthetic model proteins: Contribution of hydrophobic residues and disulfide bonds to protein stability. Peptide Research 3: 123-137 (1990).

1985-1989

  1. Hodges, R.S., P.D. Semchuk, A.K. Taneja, C.M. Kay, J.M.R. Parker and C.T. Mant. Protein design using model synthetic peptides. Peptide Research 1, 19-30 (1988).
  2. Gillespie, L.L., C. Argan, A.K. Taneja, R.S. Hodges, K.B. Freeman and G.C. Shore. A synthetic signal peptide blocks import of precursor proteins destined for the mitochondrial inner membrane or matrix. J. Biol. Chem. 260: 16045-16048 (1985).

1980-1984

  1. Lau, S.Y.M., A.K. Taneja and R.S. Hodges. Synthesis of a model protein of defined secondary and quaternary structure: Effect of chain length on the stabilization and formation of two-stranded a-helical coiled-coils. J. Biol. Chem. 259: 13253-13261 (1984).
  2. Hofmann, T., R.S. Hodges and M.N.G. James. Effect of pH on the activities of pencillopepsin and Rhizopus-pepsin and a proposal for the productive substrate binding mode in pencillopepsin. Biochemistry 23: 635-643 (1984).
  3. Talbot, J.A. and R.S. Hodges. Tropomyosin: A model protein for studying coiled-coil and a-helix stabilization. Acc. Chem. Res. 15: 224-230 (1982).
  4. Hodges, R.S., A.K. Saund, P.C.S. Chong, S.A. St.-Pierre and R.E. Reid. Synthetic model for two-stranded a-helical coiled-coils. Design, synthesis and characterization of an 86-residue analog of tropomyosin. J. Biol. Chem. 256: 1214-1224 (1981).

​ 1975-1979

  1. Hodges, R.S. Synthetic a-helical coiled-coils. Polymer Preprints 20: 51-54 (1979).
  2. St.-Pierre, S.A. and R.S. Hodges. The solution synthesis of sequential polypeptides as models for the double-stranded coiled-coil structure of tropomyosin. Can. J. Biochem. 55: 636-643 (1977).
  3. Sodek, J., R.S. Hodges and L.B. Smillie. Amino acid sequence of rabbit skeletal muscle a-tropomyosin. J. Biol. Chem. 253: 1129-1136 (1978).

1970-1974

  1. Hodges, R.S. and R.B. Merrifield. A synthetic study of the effect of tyrosine at position 120 of ribonuclease. Int. J. Peptide Prot. Res. 6: 397-405 (1974).
  2. Merrifield, R.B. and R.S. Hodges. Synthetic approaches to the study of proteins. Proceedings of the International Symposium on Macromolecules, Rio de Janeiro, 1974. Elsevier: Amsterdam (1975), pp. 417-431.
  3. Hodges, R.S. and R.B. Merrifield. The role of serine-123 in the activity and specificity of ribonuclease-reactivation of ribonuclease 1-118 by the synthetic COOH-terminal tetradeca-peptide; ribonuclease 111-124 and its O-methyl serine and alanine analogs. J. Biol. Chem. 250: 1231-1241 (1975).
  4. St.-Pierre, S.A. and R.S. Hodges. A sequential polyheptapeptide as a model for the double-stranded a-helical coiled-coil structure of tropomyosin. Biochem. Biophys. Res. Commun. 72: 581-588 (1976).
  5. Hodges, R.S. and L.B. Smillie. Chemical evidence for chain heterogeneity in rabbit muscle tropomyosin. Biochem. Biophys. Res. Commun. 41: 987-994 (1970).
  6. Hodges, R.S. and L.B. Smillie. Cysteine sequences of rabbit skeletal tropomyosin. Can. J. Biochem. 50: 330-343 (1972).
  7. Hodges, R.S. and L.B. Smillie. The histidine and methionine sequences of rabbit skeletal tropomyosin. Can. J. Biochem. 50: 312-329 (1972).
  8. Hodges, R.S., J. Sodek and L.B. Smillie. The cyanogen bromide fragments of rabbit skeletal tropomyosin. Biochem. J. 128: 102P (1972).
  9. Hodges, R.S., J. Sodek, L.B. Smillie and L. Jurasek. Tropomyosin: amino acid sequence and coiled-coil structure. Cold Spring Harbor Symp. Quant. Biol. 37: 299-310 (1972).
  10. Sodek, J., R.S. Hodges, L.B. Smillie and L. Jurasek. Amino acid sequence of rabbit skeletal tropomyosin and its coiled-coil structure. Proc. Nat. Acad. Sci. U.S.A. 69: 3800-3804 (1972).
  11. Hodges, R.S. and L.B. Smillie. Cyanogen bromide fragments of rabbit skeletal tropomyosin. Can. J. Biochem. 51: 56-70 (l973).

Proceedings Publications

2015-2019

N/A

2010-2014

  1. Kirwan, J.P. and R.S. Hodges. Global versus regional stability in tropomyosin: propagation of single-mutation effects through a rod-like protein. In Peptides: Building Bridges (M. Lebl, Ed.), Proceedings of the 22nd American Peptide Symposium, San Diego, CA, pp. 140-141 (2011).

2005-2009

  1. Kirwan, J.P., S.C. Kwok, S. McReynolds, J. Mills, D. Osguthorpe and R.S. Hodges. Unique Role of Clusters of Electrostatic Attractions in Controlling the Stability of Two-stranded a-Helical Coiled-coils. In Peptides for Youth, Proceedings of the 20th American Peptide Symposium, Montreal, Quebec, Canada (2007). (S. Del Valle, E. Escher, W.D. Lubell, (Eds) Springer p. 77-78 (2009) and Adv. Exp. Med. Biol. 611: 77-78 (2009).
  2. Kirwan, J.P., S.C. Kwok, D. Osguthorpe and R.S. Hodges. Stability control sites in two-stranded a-helical coiled-coils. Proceedings of the 4th International Peptide Symposium in conjunction with the 7th Australian peptide Conference and the 2nd Asia-Pacific International Peptide Symposium, Cairns, Queensland, Australia (2007) (http:// www.peptideoz.org) K220 (2008).
  3. Mills, J.B., S.C. Kwok, L.B. Smillie and R.S. Hodges. Identification of a Unique Stability Propagation Site that Controls Protein Stability of a-Tropomyosin: a two-stranded a-helical coiled-coil. In Understanding Biology Using Peptides: Proceedings of the 19th American Peptide Symposium. San Diego, CA (2005) (S.E. Blondelle, Ed.) Springer Science, New York, NY pp 581-582 (2006).
  4. Zoetewey, D.L., D.N.M. Jones, J.M. Wood and R.S. Hodges. Preliminary NMR Analysis of ProP 440-500 the C-terminal Cytoplasmic Domain of Bacterial Osmosensory Protein ProP. In Understanding Biology Using Peptides: Proceedings of the 19th American Peptide Symposium. San Diego, CA (2005) (S.E. Blondelle, Ed.) Springer Science, New York, NY pp 258-260 (2006).

2000-2004

  1. Zoetewey, D.L., B. Tripet, T.G. Kutateladze, M.J. Overduin, J.M. Wood and R.S. Hodges. Cytoplasmic domain of E. coli ProP forms an antiparallel coiled-coil as determined by NMR spectroscopy. In Peptide Revolution: Genomics, Proteomics and Therapeutics, Proceedings of the Eighteenth American Peptide Symposium Boston, MA (2003) (M. Chorev and T. K. Sawyer, Eds.) American Peptide Society pp. 301-302 (2004).
  2. Lu, S.M., S.C. Kwok and R.S. Hodges. Importance of hydrophobic clusters on protein folding and stability. In Peptide Revolution: Genomics, Proteomics and Therapeutics, Proceedings of the Eighteenth American Peptide Symposium Bobston, MA (2003) (M. Chorev and T. K. Sawyer, Eds.) American Peptide Society pp. 409-411 (2004).
  3. Kwok, S.C. and R.S. Hodges. Effect of chain length on coiled-coil stability: Decreasing stability with increasing chain length. In Peptide Revolution: Genomics, Proteomics and Therapeutics, Proceedings of the Eighteenth American Peptide Symposium Boston, MA (2003) (M. Chorev and T. K. Sawyer, Eds.) American Peptide Society pp. 490-492 (2004).
  4. Chen, Y., C.T. Mant and R.S. Hodges. The determination of helix stability coefficients using D-amino acid substitutions in the non-polar face of an amphipathic a-helical model peptide. In“Peptides: The Wave of the Future”, Proceedings of the Second International/Seventeenth American Peptide Symposium (M. Lebl and R.A. Houghten, Eds.), Kluwer Academic Publishers, pp. 353-354 (2001).
  5. Chana, M., B. Tripet and R.S. Hodges. The role of unstructured highly charged regions on the stability and specificity of dimerization of two-stranded a-helical coiled-coils: Neck region of kinesin-like motor protein Kif3A. In “Peptides: The Wave of the Future”, Proceedings of the Second International/Seventeenth American Peptide Symposium (M. Lebl and R.A. Houghten, Eds.), Kluwer Academic Publishers, pp. 359-360 (2001).
  6. Tripet, B. and R.S. Hodges. A Leu-Thr-Trp-Lys “lock” stabilizes the N-terminus of the kinesin neck coiled-coil. In “Peptides: The Wave of the Future”, Proceedings of the Second International/Seventeenth American Peptide Symposium (M. Lebl and R.A. Houghten, Eds.), Kluwer Academic Publishers, pp. 361-362 (2001).
  7. Tripet, B. and R.S. Hodges. STABLECOIL: An algorithm designed to predict the location and relative stability of coiled-coils in native protein sequences. In “Peptides: The Wave of the Future”, Proceedings of the Second International/Seventeenth American Peptide Symposium (M. Lebl and R.A. Houghten, Eds.), Kluwer Academic Publishers, pp. 365-366 (2001).
  8. Kwok, S.C., C.T. Mant and R.S. Hodges. Lactam-bridged and disulfide-bridged peptide mimic of a stable a-helical folded protein. In “Peptides: The Wave of the Future”, Proceedings of the Second International/Seventeenth American Peptide Symposium (M. Lebl and R.A. Houghten, Eds.), Kluwer Academic Publishers, pp. 377-378 (2001).
  9. Lu, S.M., J.R. Litowski, B. Tripet and R.S. Hodges. Homostranded and heterostranded a-helical templates for combinatorial library display: Differences in stability and solubility. In “Peptides: The Wave of the Future”, Proceedings of the Second International/Seventeenth American Peptide Symposium (M. Lebl and R.A. Houghten, Eds.), Kluwer Academic Publishers, pp. 466-467 (2001).
  10. Litowski, J.R. and R.S. Hodges. Designing heterodimeric a-helical coiled-coils: The effect of chain length on protein folding, stability and specificity. In Peptides 2000, Proceedings of the 26th European Peptide Symposium (J. Martinez and J.A. Fehrentz, eds.). EDK Publishers, Paris, France. pp. 499-500 (2001).
  11. Kwok, S.C., C.T. Mant and R.S. Hodges. Importance of secondary structure specificity determinants in protein folding and stability. In Peptides for the New Millennium”, Proceedings of the Sixteenth American Peptide Symposium (G.B. Fields, J.P. Tam and G. Barany, Eds.), Kluwer Academic Publishers, pp. 277-279 (2000).
  12. Litowski, J.R. and R.S. Hodges. The design of heterodimeric coiled-coil domains for diagnostic display systems. In “Peptides for the New Millennium”, Proceedings of the Sixteenth American Peptide Symposium (G.B. Fields, J.P. Tam and G. Barany, Eds.), Kluwer Academic Publishers, pp. 285-286 (2000).
  13. Lee, D.L., Y. Chen, K.C. Wagschal, S. McKenna, B. Harland, C.T. Mant and R.S. Hodges. Effect of D-amino acid substitutions on amphipathic -helical structure. In Peptides for the New Millennium”, Proceedings of the Sixteenth American Peptide Symposium (G.B. Fields and G. Barany, Eds.), Kluwer Academic Publishers, pp. 289-290 (2000).
  14. Yu, B.Y., P. Lavigne, P. Privalov and R.S. Hodges. Rotamer number revealed as another parameter to gauge the quality of packing in folded proteins. In Peptides for the New Millennium”, Proceedings of the Sixteenth American Peptide Symposium (G.B. Fields, J.P. Tam and G. Barany, Eds.), Kluwer Academic Publishers, pp. 318-319 (2000).

1995-1999

  1. Houston, M.E., R.T. Irvin and R.S. Hodges. Design and synthesis of a lactam bridged stabilized coiled-coil template for library display. In Peptide Science - Present and Future, Proceedings of the First International Peptide Symposium. Kluwer Academic Publishers, Y. Shimonishi (Ed.), pp. 128-131 (1999).
  2. Kwok, S.C., C.T. Mant and R.S. Hodges. Effects of a-helical and b-sheet propensities of amino acids on protein stability. In Peptides 98, Proceedings of the 25th European Peptide Symposium (Bajusz, S., and Hudecz, F., Eds.). Publisher: Akadémiai Kiadó, Budapest, pp. 34-35 (1999).
  3. Houston, M.E., H. Chao, M.C. Loewen, F.D. Sonnichsen, C.M. Kay, B.D. Sykes and R.S. Hodges. A New paradigm for fish antifreeze protein binding to ice. In Peptides: Frontiers of Peptide Science, Proceedings of the Fifteenth American Peptide Symposium (J. Tam and P. Kaumaya, Eds.) Kluwer Academic Publishers, pp. 747-748 (1999).
  4. Lavigne, P., L.H. Kondejewski, M.E. Houston, R.S. Hodges and C.M. Kay. On the energetics of the heterodimerization of Max and c-Myc Leucine Zippers. In Peptides: Frontiers of Peptide Science, Proceedings of the Fifteenth American Peptide Symposium (J. Tam and P. Kaumaya, Eds.) Kluwer Academic Publishers, pp. 467-468 (1999).
  5. Wagschal, K.C., B. Tripet, P. Lavigne and R.S. Hodges. De Novo design of a-helical coiled-coils: the effect on stability of amino acid substitution in the hydrophobic core. In Peptides: Frontiers of Peptide Science, Proceedings of the Fifteenth American Peptide Symposium (J. Tam and P. Kaumaya, Eds.) Kluwer Academic Publishers, pp. 82-84 (1999).
  6. Kohn, W.D., C.M. Kay and R.S. Hodges. Metal ion-induced folding of a de novo designed a-helical coiled-coil. In Peptides: Frontiers of Peptide Science, Proceedings of the Fifteenth American Peptide Symposium (J. Tam and P. Kaumaya, Eds.) Kluwer Academic Publishers, pp. 134-135 (1999).
  7. Houston, M.E., C.M. Kay and R.S. Hodges. Lactam bridge stabilization of a-helices and enhancement of dimerization. In: Peptides: Chemistry, Structure and Biology, Proceedings of the Fourteenth American Peptide Symposium (P. Kaumaya and R.S. Hodges, Eds.) Mayflower Scientific Ltd., England, pp. 549-551 (1996).
  8. Kohn, W.D., O.D. Monera, C.M. Kay and R.S. Hodges. The effects of different salts on the role of interhelical electrostatic repulsions in the stability of two-stranded a-helical coiled-coils. In: Peptides: Chemistry, Structure and Biology, Proceedings of the Fourteenth American Peptide Symposium (P. Kaumaya and R.S. Hodges, Eds.) Mayflower Scientific Ltd., England, pp. 829-830 (1996).
  9. Lavigne, P., L.H. Kondejewski, M.E. Houston, F.D. Sönnichsen, R.S. Hodges and C.M. Kay. Synthetic max and c-myc leucine zippers preferentially form a heterodomeric parallel coiled-coil. In: Peptides: Chemistry, Structure and Biology, Proceedings of the Fourteenth American Peptide Symposium (P. Kaumaya and R.S. Hodges, Eds.) Mayflower Scientific Ltd., England, pp. 863-864 (1996).
  10. Tripet, B., N. Zhou, F. Sönnichsen and R.S. Hodges. Hybritein 1: A de novo designed protein displaying cooperative interactions between a metal binding loop and a helix-helix dimerization motif. In "Peptides 1994", Proceedings of the 23rd European Peptide Symposium (H.L.S. Maia, Ed.), Escom Science Publishers, Leiden, The Netherlands, pp. 79-80 (1995).

1990-1994

  1. Monera, O.D., N.E. Zhou, C.M. Kay and R.S. Hodges. Parallel or antiparallel alignment of a-helical chains in two-stranded coiled-coils is controlled by interchain electrostatic interactions. In: Peptides: Chemistry, Structure and Biology, Proceedings of the Thirteenth American Peptide Symposium (R.S. Hodges and J.A. Smith, Eds.), Escom Science Publishers, Leiden, The Netherlands, pp.1057-1059 (1994).
  2. Zhou, N.E., C.M. Kay and R.S. Hodges. The role of interchain ionic interactions in protein folding and stability of two-stranded a-helical coiled-coils. In: Peptides: Chemistry, Structure and Biology, Proceedings of the Thirteenth American Peptide Symposium (R.S. Hodges and J.A. Smith, Eds.), Escom Science Publishers, Leiden, The Netherlands, pp.1069-1071 (1994).
  3. Zhou, N.E., B.-Y. Zhu, C.M. Kay and R.S. Hodges. Importance of intra-chain ionic interactions in stabilizing a-helices in proteins. In Peptides: Biology and Chemistry (Proceedings of the 1992 Chinese Peptide Symposium), (Y.-C. Du, J.P. Tam and Y.-S. Zhang, Eds.), Escom Science Publishers, Leiden, The Netherlands, pp.217-220 (1993).
  4. Zhou, N.E., C.M. Kay and R.S. Hodges. Synthetic model proteins: Positional effects of interchain a-helical hydrophobic interactions on protein conformation and stability. In "Peptides: Chemistry and Biology", Proceedings of the 12th American Peptide Symposium (J. Smith and J.E. Rivier, Eds.) Escom Science Publishers, The Netherlands (1992) 323-325.
  5. Semchuk, P.D., C.M. Kay and R.S. Hodges. Synthetic a-helical model proteins: Contribution of hydrophobic residues to protein stability. In "Peptides: Chemistry, Structure and Biology". Proceedings of the Eleventh American Peptide Symposium (J.E. Rivier and G.R. Marshall, Eds.), Escom Science Publishers, The Netherlands (1990) pp. 566-570.

1975-1979

  1. Hodges, R.S., S.A. St.-Pierre and F.-S. Tjoeng. Synthetic sequential polyheptapeptides as models for the two-stranded a-helical coiled-coil structure of tropomyosin. In "Peptides - Proceedings of the Fifth American Peptide Symposium (Eds. Goodman, M. and J. Meienhofer) John Wiley & Sons, Inc., pp. 411-414 (1977).​

Biochemistry and Molecular Genetics

CU Anschutz

Research I South

12801 East 17th Avenue

Mail Stop 8101

Aurora, CO 80045

303-724-3201

School of Medicine
General
Students
CMS Login