John Janetzko, PhD
Assistant Professor
Education:
H.B.Sc., University of TorontoPh.D., Harvard University
Graduate Program Memberships:
Courtesy Appointments in: Department of Pharmacology and Department of Pharmaceutical Sciences (Skaggs School of Pharmacy).
Laboratory of Signal Transduction and Chemical Biology
G protein-coupled receptors (GPCRs) for hormones and neurotransmitters evolved to be the most important means of communication between cells and tissues in higher organisms. They are responsive to a wide range of stimuli, from light to small molecules and proteins. This tremendous functional versatility is accomplished by a common seven-transmembrane structure. As a result of their extensive influence over human physiology and behavior, a third of all FDA-approved drugs target GPCRs. Yet, over half of non-olfactory GPCRs have not been therapeutically targeted.
The focus of my laboratory is two-fold. 1. We aim to understand the molecular mechanisms governing the function and regulation of GPCRs; 2. We aim to leverage our mechanistic understanding for the development of new strategies for targeting GPCRs in human disease.
My lab accomplishes this using a range of (bio)chemical, biophysical, and cell biological techniques. To structurally characterize our systems, we use cryo-EM, single-molecule fluorescence imaging, and mass spectrometry. Our work is truly at the frontier of mechanistic basic science and translation, and we are fortunate to have many fantastic collaborators to support our work. Ultimately, our mission is to develop the next generation of GPCR-targeting therapeutics.
| Picture | First Name | Last Name | Job Title | |
|---|---|---|---|---|
| Christopher | Markgraf | RSP | christopher.markgraf@cuanschutz.edu | |
 | Erin | Marsh | RSP |
|
| Jesse | Hudspeth | Postdoc |
|
For an up-to-date list of publications, please check MyNCBI Bibliography
(†corresponding author, *equal contribution).
Pre-prints:
- Ashley N. Ives*, Kevin Jooß*, Rafael D. Melani, Ryan T. Fellers, John Janetzko†, Neil L. Kelleher† “Capillary electrophoresis-mass spectrometry resolves proteoforms of an intact G protein-coupled receptor” ChemRxiv 2025 February. DOI: 10.26434/chemrxiv-2025-t2dr4.
- John Janetzko, Ryoji Kise, Benjamin Barsi-Rhyne, Dirk H. Siepe, Franziska M. Heydenreich, Kouki Kawakami, Matthieu Masureel, Shoji Maeda, K. Christopher Garcia, Mark von Zastrow, Asuka Inoue† and Brian K. Kobilka† “Membrane phosphoinositides stabilize GPCR-β-arrestin complexes and provide temporal control of complex assembly and dynamics”, BioRxiv 2021 October. DOI: 10.1101/2021.10.09.463790.
- Cassandra M. Joiner, Forrest A. Hammel, John Janetzko and Suzanne Walker“Protein substrates engage the lumen of O-GlcNac transferase’s tetratricopeptide repeat domain in different ways” BioRxiv 2020 December. DOI: 10.1101/2020.12.22.423982.
Peer-reviewed papers:
- Jonathan Pacheco, Karina A. Peña, Sofya Savransky, Alexandre Gidon, Gerald R.V. Hammond, John Janetzko, Jean-Pierre Vilardaga† “Fast-diffusing receptor collisions with slow-diffusing peptide ligand assemble the ternary parathyroid hormone-GPCR-arrestin complex”, Nature Communications, 2024, 15, 10499.
- Sarah C. Potter, Bettine E. Gibbs, Forrest A. Hammel, Cassandra M. Joiner, Joao A. Paulo, John Janetzko, Zebulon G. Levine, George Q. Fei, Stephen J. Haggarty, Suzanne Walker† “Dissecting OGT’s TPR domain to identify determinants of cellular function”, Proceedings of the National Academy of Sciences, 2024, 121 (22), e2401729121.
- John Janetzko*†, Cory P. Johnson*†, Paula Morales*†, Magdalina M. Sharf*† “Viewpoint on the Second Transatlantic GPCR Symposium for Early-Career Investigators”, ACS Pharmacology & Translational Science, 2023, 6, 195–199.
- John Janetzko, Ryoji Kise, Benjamin Barsi-Rhyne, Dirk H. Siepe, Franziska M. Heydenreich, Kouki Kawakami, Matthieu Masureel, Shoji Maeda, K. Christopher Garcia, Mark von Zastrow, Asuka Inoue† and Brian K. Kobilka† “Membrane phosphoinositides stabilize GPCR-β-arrestin complexes and provide temporal control of complex assembly and dynamics”, Cell, 2022, 185, 4560–4573.
- Cassandra M. Joiner, Forrest A. Hammel, John Janetzko and Suzanne Walker† “Protein Substrates Engage the Lumen of O-GlcNAc Transferase’s Tetratricopeptide Repeat Domain in Different Ways”, Biochemistry, 2021, 60 (11), 847–853.
- Weijiao Huang*, Matthieu Masureel*, Qianhui Qu*, John Janetzko*, Asuka Inoue, Hideaki E. Kato, Michael J.Robertson, Khanh C. Nguyen, Jeffrey S. Glenn, Georgios Skiniotis† and Brian K. Kobilka† “Structure of the neurotensin receptor 1 in complex with β-arrestin 1”, Nature, 2020, 579, 303–308.
- Sara E.S. Martin*, Zhi-Wei Tan*, Harri M. Itkonen, Damien Y. Duveau, Joao A. Paulo, John Janetzko, Paul L. Boutz, Lisa Törk, Frederick A. Moss, Craig J. Thomas, Steven P. Gygi, Michael B. Lazarus† and Suzanne Walker† “Structure-Based Evolution of Low Nanomolar-O-GlcNAc Transferase Inhibitors”, Journal of the American Chemical Society, 2018, 140 (42), 13542–13545.
- John Janetzko and Suzanne Walker† “Aspartate Glycosylation Triggers Isomerization to Isoaspartate”, Journal of the American Chemical Society, 2017, 139 (9), 3332–3335.
- John Janetzko, Sunia A. Trauger, Michael B. Lazarus and Suzanne Walker† “How the glycosyltransferase OGT catalyzes amide bond cleavage”, Nature Chemical Biology, 2016, 12 (11), 899–901.
- Jordan D. Goodreid, John Janetzko, John P. Santa Maria Jr., Keith S. Wong, Elisa, Leung, Bryan T. Eger, Steve Bryson, Emil F. Pai, Scott D. Gray-Owen, Suzanne Walker, Walid A. Houry and Robert A. Batey† “Development and Characterization of Potent Cyclic Acyldepsipeptide Analogues with Increased Antimicrobial Activity”, Journal of Medicinal Chemistry, 2016, 59 (2), 624–646.
- Rodrigo F. Ortiz-Meoz, Jiaoyang Jiang, Michael B. Lazarus, Marina Orman, John Janetzko, Chenguang Fan, Damien Y. Duveau, Zhi-Wei Tan, Craig J. Thomas and Suzanne Walker† “A Small Molecule That Inhibits OGT Activity in Cells”, ACS Chemical Biology, 2015, 10 (6), 1392–1397.
- John Janetzko and Suzanne Walker† “The Making of a Sweet Modification: Structure and Function of O-GlcNAc Transferase”, Journal of Biological Chemistry, 2014, 289 (50), 34424–34432.
- John Janetzko and Robert A. Batey† “Organoboron-Based Allylation Approach to the Total Synthesis of the Medium-Ring Dilactone (+)-Antimycin A1b”, Journal of Organic Chemistry, 2014, 79 (16), 7415–7425.
- Michael B. Lazarus*, Jiaoyang Jiang*, Vaibhav Kapuria, Tanja Bhuiyan, John Janetzko, Wesley F. Zandberg, David J. Vocadlo, Winship Herr† and Suzanne Walker† “HCF-1 is cleaved in the active site of O-GlcNAc transferase”, Science, 2013, 342 (6163), 1235–1239 (*equal contribution).
- Vincent T. Annibale, Runyu Tan, John Janetzko, Liisa M. Lund, and Datong Song† “Palladium β-Diiminate Chemistry: Reactivity Towards Monodentate Ligands and Arylboronic Acids”, Inorganica Chimica Acta, 2012, 380, 308–321.
- Farhad Nowrouzi, John Janetzko and Robert A. Batey† “Indium-promoted chemo- and diastereoselective allylation of α,β-epoxyketones with potassium allyltrifluoroborate”, Organic Letters, 2010, 12 (23), 5490–5493.
- Alen Hadzovic, John Janetzko and Datong Song† “Novel Dinuclear and Trinuclear Palladium β-Diiminate Complexes Containing Amido-Chloro Double-Bridges”, Dalton Transactions, 2008, 3279–3281.