The overall objective of this proposal is to accelerate the acquisition of structural information about membrane proteins by applying a structural genomics approach informed by the collective experience of a team of expert investigators. We have established the New York Consortium on Membrane Protein Structure NYCOMPS to work together toward this objective. NYCOMPS participates as a Specialized Center in Phase 2 of the Protein Structure Initiative (PSI-2) now. As constituted for PSI-Biology, NYCOMPS will comprise 12 Principal Investigators at six institutions. Our pipeline for structure determination will select targets through a bioinformatics analysis of all known sequences, move on to recombinant DNA cloning, protein expression in bacteria or eukaryotic cells, and protein purification at moderately high throughput, and then continue on to determine structures by x-ray crystallography. Our Protein Production Facility at the New York Structural Biology Center (NYSBC) handles targets through purification at a mid-scale level;and successful candidates are distributed to participant laboratories for scale-up and crystallization. Functional analysis of structures will be performed both by computations and through routine experimental biochemistry. Targets will be identified through nominations from the biological community, including adjunct NYCOMPS members, and from NYCOMPS biological themes, which concern elucidation of the membrane protein universe and structural studies on energy homeostasis and metabolic disorders. A program in technology development will aim to improve pipeline efficiency and quality of results. The project will be managed to optimize output and to integrate effectively with the PSI-Biology network and with other membrane protein structure efforts.

Public Health Relevance

Proteins embedded in membranes are abundant (20-30% of proteins in any organism) and they perform some of the most essential of activities in biology. Their importance for biomedicine is evident as they are the molecular targets of more than 40% of all FDA-approved drugs. Yet, because membrane proteins present severe challenges for biophysical study, membrane proteins currently constitute less than 1% of known atomic-level structures.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54GM095315-03
Application #
8334048
Study Section
Special Emphasis Panel (ZGM1-CBB-3 (MP))
Program Officer
Chin, Jean
Project Start
2010-09-30
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$3,122,884
Indirect Cost
$996,894
Name
New York Structural Biology Center
Department
Type
DUNS #
011191520
City
New York
State
NY
Country
United States
Zip Code
10027
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