Abstract

Reorganization of the actin cytoskeleton allows cells to change shape and move in response to environmental cues. Polymerization of actin.is tightly regulated, and the cell maintains an arsenal of proteins to control when, where and how filaments grow. Arp2/3 complex is an assembly of seven proteins that nucleates the growth of new actin filaments in a signal-dependent manner. Nucleation promoting factors link Arp2/3 complex to upstream signals. They bind to Arp2/3 complex, recruit the first actin monomer for the new filament, and promote a activating conformational change in the complex. The goal of this proposal is to use x-ray crystallography to determine the structures of Arp2/3 complex with a bound nucleation promoting factor and with nucleation promoting factor plus actin monomer. These structures will provide a molecular basis for understanding how Arp2/3 complex nucleates the growth of new actin filaments. Furthermore, it will show how nucleation promoting factors activate the complex. This will provide a basis for a better understanding of cytoskeletal function in both normal and diseased states of the cell.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM074374-02
Application #
7076947
Study Section
Special Emphasis Panel (ZRG1-F04B (20))
Program Officer
Flicker, Paula F
Project Start
2005-06-01
Project End
2007-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$48,796
Indirect Cost

  Institution

Name
Yale University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520