Francisco Asturias, PhD
Professor
Contact Information
Fax: (303) 724-1624
E-mail: Francisco.Asturias@cuanschutz.edu
Graduate Program Memberships
Many essential cellular processes are carried out by "macromolecular machines", large assemblies that include tens of different proteins, each contributing in a specific manner to the structure and function of the machine. Characterization of these intricate macromolecular complexes using a combination of techniques constitutes the next frontier in structural biology.
Despite including many different proteins, macromolecular complexes often display minimal enzymatic activity. This suggests that conformational changes and interactions are fundamental to their molecular mechanism. My group uses cryo-electron microscopy to characterize the structure, conformational states and interactions of macromolecular complexes involved in essential cellular processes. We correlate that structural information with biochemical and functional data to establish the mechanism of these remarkable cellular machines.
| Pictures | First Name | Last Name | Job Title | |
|---|---|---|---|---|
 | Naseer | Iqbal | Postdoctoral Scholar | Naseer.Iqbal@cuanschutz.edu |
 | Jenny (Jiaqin) | Li | Postdoctoral Scholar | Jiaqin.Li@cuanschutz.edu |
 | Russell | McFarland | Core Manager - Cryo-EM | russell.mcfarland@cuanschutz.edu |
 | Haiyan | Zhao | Senior Research Instructor | Haiyan.Zhao@cuanschutz.edu |
2014
Tsai, K.L., Tomomori-Sato, C., Sato, S., Conaway, R.C., Conaway, J.W., and Asturias, F.J. 2014. Subunit architecture and functional modular rearrangements of the transcriptional Mediator complex
Cell 157:1430-1444.
2013
Minnihan, E.C., Ando, N., Brignole, E.J., Olshansky, L., Chittuluru, J., Asturias, F.J., Drennan, C.L., Nocera, D.G., Stubbe, J. 2013. Generation of a stable, aminotyrosyl radical-induced α2β2 complex of E. coli class Ia ribonucleotide reductase.
Proc Nat Acad Sci USA 110:3835-3840.
Tsai, K.L., Sato, S., Tomomori-Sato, C., Conaway, R.C., Conaway, J.W., and Asturias, F.J. 2013. A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction
Nat Struct Mol Biol 20:611-619.
Lai YT, Tsai KL, Sawaya MR, Asturias FJ, Yeates TO. Structure and flexibility of nanoscale protein cages designed by symmetric self-assembly 2013
J Am Chem Soc 135:7738-43.
2012
Cai, G., Chaban, Y., Imasaki, T., Kovacs, J.A., Calero, G., Penczek, P.A., Takagi, Y., and Asturias, F.J. 2012. Interaction of the Mediator Head module with RNA polymerase II
Structure 20:899-910.
Gibbons, B.J., Brignole, E.J., Azubel, M., Murakami, K., Voss, N.R., Bushnell, D. Asturias, F.J., and Kornberg, R.D. 2012. Subunit Architecture of General Transcription Factor TFIIH
Proc Nat Acad Sci U S A 109:1949-1954.
Yang, Z., Fang, J., Chittuluru, J., Xu, F. Asturias, F.J., and Penczek, P.A. 2012. Iterative stable alignment and clustering of 2D transmission electron microscope images
Structure 20:237-247.
Zimanyi, C.M., Ando, N., Brignole, E.J., Asturias, F.J., Stubbe, J, Drennan, C.L..2012. Tangled up in knots – Structures of inactivated forms of Escherichia coli class Ia Ribonucleotide Reductase
Structure 20:1374-1383.
Aye Y., Brignole, E.J., Long, M.J., Chittuluru, J., Drennan, C.L., Asturias, F.J., Stubbe, J. 2012. Clofarabine targets the large subunit (α) of human ribonucleotide reductase in live cells by assembly into persistent hexamers
Chem Biol 19:799-805.
2011
Chittuluru, J.R., Chaban, Y., Monnet-Saksouk, J., Carrozza, M.J., Sapountzi, V., Selleck, W., Huang, J., Utley, R.T., Cramet, M., Allard, S., Cai, G., Workman, J.L., Fried, M.G., Tan, S., Côté, J., and. Asturias, F.J. 2011. Structure and nucleosome interaction of the yeast NuA4 and Piccolo-NuA4 histone acetyltransferase complexes
Nat Struct Mol Biol 18:1196-203.
Imasaki, T, Calero, G, Cai, G, Tsai,K-L, Yamada, K, Cardelli, F, Erdjument-Bromage, H, Tempst, P, Berger, I, Lorch Kornberg, G, Asturias, FJ, Kornberg, RD, and Takagi, Y. 2011. Architecture of the Mediator head module. Nature,
Nature 475:240-243.
Wang, W., Perovic, I., Chittuluru, J., Kaganovich, A., Nguyen, L.T., Liao, J., Auclair, J.R., Johnson, D., Landeru A., Simorellis, A.M., Ju, S., Cookson, M.R., Asturias, F.J., Agar, J.N., Webb, B.N., Kang, C., Ringe, D., Petsko, G.A., Pochapsky, T.C., and Hoang, Q.Q. 2011. A soluble α-synuclein construct forms a dynamic tetramer
Proc Nat Acad Sci U S A 108:17797-802.
Ando, N., Brignole, E.J., Stock, C.M., Funk, M.A., Yokoyama, K., Asturias, F.J., Stubbe, J., Drennan, C. 2011. Structural interconversions modulate activity of E. coli ribonucleotide reductase
Proc Nat Acad Sci U S A 108:21046-51.
2010
Cai, G., Imasaki, T., Yamada, K., Cardelli, F., Takagi, Y. and F.J. Asturias 2010. Mediator Head module Structure and Functional Interactions
Nat Struct Mol Biol 17:273-279.
Lee, J.H., Cai, G, Panigrahi, A., Dunham-Ems, S., Nguyen, T.N., Radolf, J.A., Asturias, F.J. and Günzl, A. 2010. TFIIH-associated mediator head is a basal factor of small nuclear spliced leader RNA gene transcription in early-diverged trypanosomes
Mol Cell Biol 30: 5502-5513.
Opalka, N., Brown, J. Lane, W.J., Twist, K-A .F., Landick, R., Asturias, F.J. and Darst., S.A. 2010. Complete structural model of Escherichia coli RNA polymerase from a hybrid approach
PloS Biol 8: 1-16.
2009
Cai, G., Imasaki, T., Takagi, Y. and F.J. Asturias 2009. Mediator structural conservation and implications for the regulation mechanism
Structure 17:559-567.
Brignole, E.J., Smith, S., and F.J. Asturias 2009. Conformational Flexibility of Metazoan Fatty Acid Synthase Enables Catalysis
Nat Struct Mol Biol 16:190-197
Asturias F.J. 2009. TFIID: A closer look highlights its complexity
Structure 17:1323-1324.
2008
Chaban, Y.L., Ezeokonkwo, C., Chung, W.H., Zhang, F., Kornberg, R.D., Maier-Davis, B., Lorch, Y., and F.J. Asturias 2008. Structure of a RSC-Nucleosome Complex and Insights into Chromatin Remodeling
Nat Struct Mol Biol 15:1272-1277.
Fuxreiter, M., Tompa, P., Simon, I., Uversky, V.N., Hansen, J.C., and F.J. Asturias 2008. Malleable machines take shape in eukaryotic transcriptional regulation
Nat Chem Biol 4:728-737.
Shaikh, T.R., Gao, H., Baxter, W.T., Asturias, F.J., Boisset, N., Leith, A., and J. Frank 2008. SPIDER Image Processing for Single-Particle Reconstruction of Biological Macromolecules from Electron Micrographs
Nat Protocols 3:1941-1974.
Yang, C., Penczek, P., Leith, A., Asturias, F., J., Ng, E. G., Glaeser, R. M., and J. Frank 2008. The Parallelization of SPIDER on Distributed-Memory Computers Using MPI.
J Struct Biol 157:240-249.
2006
Takagi Y., Guillermo C., Komori H., Brown J.A., Ehrensberger A.H., Hudmon A., Asturias F.J., and R.D. Kornberg 2006. Head Module Control of Mediator Interactions
Mol Cell 23:355-364.
Asturias, F.J., Cheung, I., Sabouri, N., Chilkova, O., Wepplo, D., and E. Johansson 2006. Structure of Saccharomyces cerevisiae DNA polymerase epsilon by cryo-electron microscopy
Nat Struct Mol Biol 13:35-43.
Asturias, F. J. 2006. Mammalian Fatty Acid Synthase: X-ray Structure of a Molecular Assembly Line
ACS Chem Biol 1:135-138.
2005
Takagi, Y., Chadick, J.Z., Davis, J.A., and F.J. Asturias 2005. Preponderance of free Mediator in the yeast Saccharomyces cerevisiae
J Biol Chem. 280:31200-31207.
Chadick, J. Z. and F.J. Asturias 2005. Structure of eukaryotic Mediator complexes
Trends in Biochem Sci. 30:264-271.
Asturias, F. J., Chadick, J. Z., Cheung, I. K., Stark, H., Witkowski, A., Joshi, A. K. and S. Smith 2005. Structure and molecular organization of mammalian fatty acid synthase
Nat Struct Mol Biol. 12:225-232.
2004
F.J. Asturias 2004. RNA polymerase II structure, and organization of the preinitiation complex
Curr Opin Struct Biol. 14:121-129.
Bourbon, H.M., et al. 2004. A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II
Mol Cell. 14:553-557.
Witkowski, A., Ghosal, A., Joshi, A. K., Witkowska, H. E., Asturias, F. J. and S. Smith 2004. Head-to-head coiled arrangement of the subunits of the animal fatty acid synthase
Chem Biol. 11:1667-1676.
F.J. Asturias 2004. Another piece in the transcription initation puzzle
Nat Struct Mol Biol. 11:1031-1033.
2003
Asturias, F.J., and J.L. Craighead 2003. RNA polymerase II at initiation
PNAS. 100:6893-6895.
Chung, W.H., Craighead, J.L., Chang, W.H., Ezeokonkwo, C., Bareket-Samish, A., Kornberg, R.D., and F.J. Asturias 2003. RNA Polymerase II/TFIIF Structure and Conserved Organization of the Initiation Complex
Mol Cell. 12:1003-1013.
2002
Asturias, F. J., Ezeokonkwo, C., Kornberg, R. D. and Y. Lorch 2002. Electron microscopic analysis of the RSC chromatin remodeling complex
Meth Enzymol. 376:48-62.
Asturias, F. J., Chung, W. H., Kornberg, R. D. and Y. Lorch 2002. Structural analysis of the RSC chromatin-remodeling complex
PNAS. 99:13477-13480.
Joshua A. Davis, Yuichiro Takagi, Roger D. Kornberg, and F. J. Asturias 2002. Structure of the yeast RNA polymerase II holoenzyme: Mediator conformation and polymerase interaction
Mol Cell. 10:409-415.
Craighead, J., Chang, W. and F.J. Asturias 2002. Structure of Yeast RNA Polymerase II in Solution. Implications for Enzyme Regulation and Interaction with Promoter DNA
Structure (Camb). 10:1117-1125.
2000
Dotson, M. R., Yuan, C. X., Roeder, R. G., Myers, L. C., Gustafsson, C. M., Jiang, Y. W., Li, Y., Kornberg, R. D. and F.J. Asturias 2000. Structural organization of yeast and mammalian mediator complexes
PNAS. 97:14307-14310.
1999
Asturias, F.J., Y.W. Jiang, L.C. Myers, C.M. Gustafsson and R.D. Kornberg 1999. Conserved structures of mediator and RNA polymerase II holoenzyme
Science. 283:985-987.
Asturias, F.J. and R.D. Kornberg. 1999. Protein crystallization on lipid layers and structure determination of the RNA polymerase II transcription initiation complex
J. Biol. Chem.. 274:6813-6816.
1997
Asturias F.J., W. Chang, Y. Li and R.D. Kornberg. 1997. Electron cyrstallography of yeast RNA polymerase II preserved in vitreous ice
Ultramicroscopy. 70:133-143.
Asturias, F.J., G.D. Meredith, C.L. Poglitsch and R.D. Kornberg. 1997. Two conformations of RNA polymerase I I revealed by electron crystallography
J. Mol. Biol. 272:536-540.