Structural Genomics on Membrane Proteins

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(Restricted aspirations throughout) Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. 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. As constituted for PSI-Biology, NYCOMPS will comprise ten Principal Investigators at five institutions. Our pipeline for structure determination will select targets through a bioinformatics analysis of known sequences, move on to recombinant DNA cloning, protein expression in bacteria or eukaryotic cells, and protein purification at moderately high throughput, and then proceed 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. Minimal 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. Technology development will be limited to direct improvements in pipeline efficiency. The project will be managed to optimize output and to integrate effectively with the PSI-Biology network and with other membrane protein structure efforts.