The long-term goal of this proposal is to understand the structural principles that govern the interactions among proteins. The focus is on the coiled coil, a simple, widespread, helical oligomerization motif. This research will define the basis for the specificity of coiled-coil associations and investigate the structures of coiled coil proteins.
The specific aims of the research are: 1.- Determine the structures and stabilities of leucine zipper variants with changes in helix number and direction to define the origins of structural specificity and uniqueness. 2.- Create peptide probes for coiled-coil domains of the tumor suppressor APC and two cell-division proteins to investigate sequence patterns that impart coiled-coil heterospecificity. 3.- Develop genetic and computational approaches to explore the basis for pairing specificity in coiled coils. 4.- Determine crystal structures of hyperthermostable and functionally critical coiled-coil proteins to investigate the relationships between structure and function of this motif. Coiled-coil proteins occur in virtually every physiological system. Understanding the design principles of this motif will clarify the roles of coiled coils in processes as varied as transcription, viral infection, force generation, cell division, and fertilization. The applicnts' research will improve structural predictions from genomic sequence data and yield new methods to target peptide ligands to virtually any coiled-coil protein. The targets of their peptide probes, APC, Eg5 and the septins, play key roles in cell division. APC is mutant in most colorectal tumors. These examples emphasize that the studies will have direct significance for molecular biology and medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM048958-12S1
Application #
6938056
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Basavappa, Ravi
Project Start
1992-06-01
Project End
2005-08-31
Budget Start
2003-06-01
Budget End
2005-08-31
Support Year
12
Fiscal Year
2004
Total Cost
$97,634
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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