CCR5 is representative of a family of G protein-coupled chemokine receptors which play important roles in human health and disease. CCR5 also serves as an obligate co-receptor for M-tropic HIV-1 infection of immune cells, a critical step in the etiology of AIDS. Determination of the structure of CCR5 would provide information of the very highest relevance both to the elucidation of the fundamental molecular mechanisms of HIV infection and in the development of AIDS therapeutic strategies. Unfortunately, progress in the experimental determination of the structure of CCR5 and other chemokine receptors has been virtually nonexistent because of the unavailability of sufficient quantities of these receptors in properly folded form for crystal growth or nuclear magnetic resonance (NMR). CCR5 can now be purified following heterologous overexpression in E. coli. However, the protein is misfolded. Because it is an integral membrane protein, methods commonly used to refold water soluble proteins expressed into inclusion bodies are not applicable to CCR5. The primary aim of this proposal is therefore to develop a method for refolding milligram quantities of purified CCR5 into its native-like conformation. Successful completion of this aim will lead directly to the initiation of high-resolution structural studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI054344-02
Application #
6666812
Study Section
Special Emphasis Panel (ZRG1-AARR-1 (46))
Program Officer
Voulgaropoulou, Frosso
Project Start
2002-09-30
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$151,000
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Biochemistry
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Myers, Jeffrey K; Beihoffer, Lauren A; Sanders, Charles R (2005) Phenotology of disease-linked proteins. Hum Mutat 25:90-7