Guanosine triphosphate-binding proteins regulate numerous processes in all cells. The types of process include synthesis, signal transduction, growth regulation and intracellular transport, and several others. These proteins vary in size and structure, but they share regions of conserved protein sequence, in their GTP-binding domains. Moreover the GTP-binding domains of two of these proteins, ras p21 and elongation factor Tu, possess nearly identical tertiary structures. The similarity of these structures suggests that GTP and GDP similarly alter the structures of these proteins and indeed those of all GTP regulatory proteins. This conclusion warrants the use of reasoning by analogy to define the functions of these proteins. The peptide chain elongation factors Tu and Ts comprise a GTP-regulatory system whose interaction with a variety of cellular components make it an informative subject both for the study of GTP-promoted processes and for the identification of protein-protein and protein-nucleic acid interactions. EF-Tu presents a useful model for these processes because it is an abundant, soluble protein of tractable size whose tertiary structure has been largely solved. EF-Tu engages in three separate but interdependent processes-GTP-mediated aatRNA-binding, ribosome-mediated GTP hydrolysis, and EF-Ts-mediated GDP exchange. Other GTP-regulatory proteins engage in analogous processes. To understand how these processes occur, we are determining how single amino acid replacements alter each of the functions. The structural consequences of these changes are determined by reference to the EF-Tu structure, and the effect of the analogous change on other GTP-regulatory proteins is predicted. The reliability of this approach can be assessed by comparing the effects of analogous changes on the functions of EF-Tu and ras p21, whose structure is also known.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM030800-09
Application #
3278689
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1982-09-01
Project End
1995-11-30
Budget Start
1991-12-15
Budget End
1992-11-30
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
New York St Off of Mr and Dev Disab
Department
Type
DUNS #
City
Albany
State
NY
Country
United States
Zip Code
12229
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