Abstract

Heterotrimeric guanine nucleotide-binding regulatory proteins (G-proteins) form a large family of signaling proteins that are involved in transitory interactions with membrane bound receptors. The subunits in heterotrimeric G-proteins are designated a (Mr 40-46 KDa), b (Mr 37 KDa), and g (Mr 8 KDa); the G-protein a subunit contains GTPase activity. The Gabg-GDP is the basal complex state and, upon an appropriate signal, GDP is released and the dissociated species Ga-GTP and bg transduces the signal downstream. After GTP hydrolysis, the Gabg-GDP is reformed and the signal is terminated. The principal investigator's group has determined the structures of several Gia species including Gia1-GDP, Gia1b1g2, and Gia1-ligand complexes. The principal investigator proposes to continue his group's studies into the structural and functional consequences of GTP hydrolysis on the Ga-GTP species, particularly in the context of signal transduction, as well as determine the structures of Gia1 complexes with RGS4 or GIAP and the structure of Gsa complexed with a adenyl cyclase core fragment..

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK046371-06
Application #
2905539
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Margolis, Ronald N
Project Start
1994-08-01
Project End
2000-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Maziarz, Marcin; Leyme, Anthony; Marivin, Arthur et al. (2018) Atypical activation of the G protein G?q by the oncogenic mutation Q209P. J Biol Chem 293:19586-19599
Sprang, Stephen R (2016) Invited review: Activation of G proteins by GTP and the mechanism of G?-catalyzed GTP hydrolysis. Biopolymers 105:449-62
Chan, Puiyee; Thomas, Celestine J; Sprang, Stephen R et al. (2013) Molecular chaperoning function of Ric-8 is to fold nascent heterotrimeric G protein ? subunits. Proc Natl Acad Sci U S A 110:3794-9
Chen, Zhe; Guo, Liang; Hadas, Jana et al. (2012) Activation of p115-RhoGEF requires direct association of G?13 and the Dbl homology domain. J Biol Chem 287:25490-500
Seifert, Roland; Lushington, Gerald H; Mou, Tung-Chung et al. (2012) Inhibitors of membranous adenylyl cyclases. Trends Pharmacol Sci 33:64-78
Thomas, Celestine J; Briknarová, Klára; Hilmer, Jonathan K et al. (2011) The nucleotide exchange factor Ric-8A is a chaperone for the conformationally dynamic nucleotide-free state of G?i1. PLoS One 6:e23197
Erdorf, Miriam; Mou, Tung-Chung; Seifert, Roland (2011) Impact of divalent metal ions on regulation of adenylyl cyclase isoforms by forskolin analogs. Biochem Pharmacol 82:1673-81
Hübner, Melanie; Dixit, Anshuman; Mou, Tung-Chung et al. (2011) Structural basis for the high-affinity inhibition of mammalian membranous adenylyl cyclase by 2',3'-o-(N-methylanthraniloyl)-inosine 5'-triphosphate. Mol Pharmacol 80:87-96
Chen, Zhe; Medina, Frank; Liu, Mu-ya et al. (2010) Activated RhoA binds to the pleckstrin homology (PH) domain of PDZ-RhoGEF, a potential site for autoregulation. J Biol Chem 285:21070-81
Palmioli, Alessandro; Sacco, Elena; Abraham, Sherwin et al. (2009) First experimental identification of Ras-inhibitor binding interface using a water-soluble Ras ligand. Bioorg Med Chem Lett 19:4217-22

Showing the most recent 10 out of 47 publications