Areas of Interest
Our lab studies the molecular basis of G protein-coupled receptor (GPCR)-mediated signal transduction, principally via the technique of X-ray crystallography. GPCRs are responsible for the sensations of sight and smell, for regulation of blood pressure and heart rate, and for many other cellular events. Extracellular signals impinging upon GPCRs in the cell membrane induce a conformational change that allows these proteins to activate specific heterotrimeric G proteins within the cell. The activated G proteins then bind to various effectors that initiate downstream cascades, leading to profound physiological change. Activated GPCRs also specifically interact with GPCR kinases (GRKs), which function to inhibit signaling by heterotrimeric G proteins and to initiate G protein-independent signaling cascades. By determining atomic structures of these signaling proteins both alone and in complex with their various targets, we provide important insights into the molecular basis of signal transduction and of diseases that emerge as a result of dysfunctional signaling.
Honors & Awards
2000 American Heart Association Texas Affiliate Lyndon Baines Johnson Research Award
2002 Cottrell Scholar Award (Research Corporation)
2004 U. of Texas at Austin College of Natural Sciences Teaching Excellence Award
2008 Basic Science Research Award (U. Michigan Medical School)
2009 John J. Abel Award (American Society for Pharmacology and Experimental Therapeutics)
2010 American Society for Biochemistry and Molecular Biology Young Investigator Award
Tesmer VM, Kawano T, Shankaranarayanan A, Kozasa T, Tesmer JJG: Snapshot of activated G proteins at the membrane: the Gαq-GRK2-Gβγ complex. Science 2005, 310: 1686-1690. PMID: 16339447.
Lodowski DT, Tesmer VM, Benovic JL, Tesmer JJG: The structure of G protein-coupled receptor kinase 6 defines a second lineage of GRKs. J. Biol. Chem. 2006, 281: 16785-93. PMID: 16613860.
Lutz S, Shankaranarayanan A, Coco C, Ridilla M, Nance MR, Vettel C, Baltus D, Evelyn CR, Neubig RR, Wieland T, Tesmer JJG: Structure of Gαq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs. Science 2007, 318:1923-7. PMID: 18096806
Singh P, Wang B, Madea T, Palczewski K, Tesmer JJG: Structures of rhodopsin kinase in different ligand states reveal key elements involved in G protein-coupled receptor kinase activation. J. Biol. Chem. 2008, 283:14053-62. PMCID: 2376226
Shankaranarayanan A, Thal DM, Tesmer VM, Roman DL, Neubig RR, Kozasa T, Tesmer JJG: Assembly of high order Gαq-effector complexes with RGS proteins. J. Biol. Chem. 2008, 283:34923-34. PMCID: 2596395
Huang C, Yoshino-Koh K, Tesmer JJG: A surface of the kinase domain critical for the allosteric activation of G protein-coupled receptor kinases. J. Biol. Chem. 2009, 284:17206-15. PMCID: 2719358.
Tesmer JJG, Tesmer VM, Lodowski DT, Steinhagen H, Huber J: Structure of human G protein-coupled receptor kinase 2 in complex with the kinase inhibitor balanol. J. Med. Chem. 2010, 53: 1867-70. PMCID: 3073382
Narasimhan D, Nance MR, Gao D, Ko M-C, MacDonald J, Tamburi P, Yoon D, Landry DM, Woods JH, Zhan C-G, Tesmer JJG, and Sunahara RK: Structural analysis of thermostabilizing mutations of cocaine esterase. Protein Eng. Des. Sel., 2010, 23: 537-47. PMCID: 2920302
Boguth CA, Singh P, Huang C, Tesmer JJG: Molecular basis for activation of G protein-coupled receptor kinases. EMBO J, 2010, 29: 3249-59. PMCID: 2957210
Thal DM, Yeow RY, Schoenau C, Huber J, Tesmer JJG: Molecular mechanism of selectivity among G protein-coupled receptor kinase 2 inhibitors. Mol. Pharm. 2011, 80: 294-303. PMCID: 3141885
Lyon AM, Tesmer VM, Dhamsania VD, Thal DM, Gutierrez J, Chowdhury S, Suddala KC, Northup JK, Tesmer JJG: An autoinhibitory helix in the C-terminal region of phospholipase Cβ mediates Gαq activation. Nature Struct. Mol. Biol. 2011, 18:999-1005. PMCID: 3168981
Aittaleb M, Nishimura A, Linder M, Tesmer JJG: Plasma membrane association of p63RhoGEF is mediated by palmitoylation and is required for basal activity in cells. J. Biol. Chem. 2011, 286:34448-56. PMCID: 3190789
Boughton AP, Yang P, Tesmer VM, Ding B, Tesmer JJG, Chen Z: Heterotrimeric G protein β1γ2 subunits change orientation upon complex formation with G protein-coupled receptor kinase 2 (GRK2) on a model membrane. Proc. Natl. Acad. Sci. U.S.A. 2011, 108: E667-73. PMCID: 3174637
For a complete list of this person’s PubMed publications, click HERE