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 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.
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.
|Yang, Tingting; Liu, Qun; Kloss, Brian et al. (2014) Structure and selectivity in bestrophin ion channels. Science 346:355-9|
|Yachdav, Guy; Kloppmann, Edda; Kajan, Laszlo et al. (2014) PredictProtein--an open resource for online prediction of protein structural and functional features. Nucleic Acids Res 42:W337-43|
|Sciara, Giuliano; Clarke, Oliver B; Tomasek, David et al. (2014) Structural basis for catalysis in a CDP-alcohol phosphotransferase. Nat Commun 5:4068|
|Liu, Qun; Guo, Youzhong; Chang, Yanqi et al. (2014) Multi-crystal native SAD analysis at 6?keV. Acta Crystallogr D Biol Crystallogr 70:2544-57|
|Huang, Hua; Levin, Elena J; Liu, Shian et al. (2014) Structure of a membrane-embedded prenyltransferase homologous to UBIAD1. PLoS Biol 12:e1001911|
|Hendrickson, Wayne A (2014) Anomalous diffraction in crystallographic phase evaluation. Q Rev Biophys 47:49-93|
|Mulligan, Christopher; Fitzgerald, Gabriel A; Wang, Da-Neng et al. (2014) Functional characterization of a Na+-dependent dicarboxylate transporter from Vibrio cholerae. J Gen Physiol 143:745-59|
|Zhou, Xiaoming; Levin, Elena J; Pan, Yaping et al. (2014) Structural basis of the alternating-access mechanism in a bile acid transporter. Nature 505:569-73|
|Chang, Yanqi; Bruni, Renato; Kloss, Brian et al. (2014) Structural basis for a pH-sensitive calcium leak across membranes. Science 344:1131-5|
|Qi, Ruifeng; Sarbeng, Evans Boateng; Liu, Qun et al. (2013) Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP. Nat Struct Mol Biol 20:900-7|
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