In the proposed studies, the investigators plan to utilized the structural information to prepare a library of specific mutations designed to systematically alter the TR LBD surface such that interactions with other proteins involved in various TR functions might be disrupted. It is also planned to prepare mutations that should influence the function of two regions termed tau-3 and tau-4 thought to be involved in TR LBD transcriptional activation functions and of a Helix region (Helix-1) that maybe involved in various TR functions. Activities of mutated molecules will be examined through assays of T3 binding (TR + T3) binding to DNA and other proteins and by transfecting genes that express the mutated TRs along with reporter genes and genes that express other proteins that interact with TRs in mammalian cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK051281-03
Application #
2701206
Study Section
Endocrinology Study Section (END)
Program Officer
Margolis, Ronald N
Project Start
1996-05-01
Project End
1999-11-30
Budget Start
1998-07-28
Budget End
1999-11-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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