My goal is to investigate the structure and function relationships of the trimeric GTP-binding proteins. The model structures of these trimers were built using the coordinates of the crystal structure of transducin alpha-beta-gamma trimer. The following aspects of the G-protein function were modeled: the residues responsible for the GDP/GTP exchange that leads to activation of the alpha subunit; the solvent accessible surface changes upon GTP/GDP exchange, by comparing the crystal structures in GTP and GDP forms; the contact surface changes related to binding of beta-gamma subunits, the receptor and the effector. The surface changes indicated by modeling are being studied by scanning mutagenesis. The modeling showed that the A336S mutation in Gs, found in two types of endocrine diseases, acts via disrupting the binding of the guanine ring. The models also helped in explaining the effects of the N-terminal and C-terminal mutations in the alpha subunit.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001081-20
Application #
2664717
Study Section
Project Start
Project End
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
20
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kozak, John J; Gray, Harry B; Garza-López, Roberto A (2018) Relaxation of structural constraints during Amicyanin unfolding. J Inorg Biochem 179:135-145
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Chu, Shidong; Zhou, Guangyan; Gochin, Miriam (2017) Evaluation of ligand-based NMR screening methods to characterize small molecule binding to HIV-1 glycoprotein-41. Org Biomol Chem 15:5210-5219
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Nguyen, Hai Dang; Yadav, Tribhuwan; Giri, Sumanprava et al. (2017) Functions of Replication Protein A as a Sensor of R Loops and a Regulator of RNaseH1. Mol Cell 65:832-847.e4
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Nekouzadeh, Ali; Rudy, Yoram (2016) Conformational changes of an ion-channel during gating and emerging electrophysiologic properties: Application of a computational approach to cardiac Kv7.1. Prog Biophys Mol Biol 120:18-27
Towse, Clare-Louise; Vymetal, Jiri; Vondrasek, Jiri et al. (2016) Insights into Unfolded Proteins from the Intrinsic ?/? Propensities of the AAXAA Host-Guest Series. Biophys J 110:348-361

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