Structural Genomics and Membrane Proteins

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 ➋a;NYCOMPS➋b; to work together toward this objective. NYCOMPS participates as a Specialized Center in Phase 2 of the Protein Structure Initiative ➋a;PSI‐2➋b; 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 ➋a;NYSBC➋b; 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 perfomed 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.