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.
| Assur Sanghai, Zahra; Liu, Qun; Clarke, Oliver B et al. (2018) Structure-based analysis of CysZ-mediated cellular uptake of sulfate. Elife 7: |
| Su, Min; Gao, Feng; Yuan, Qi et al. (2017) Structural basis for conductance through TRIC cation channels. Nat Commun 8:15103 |
| Dufrisne, Meagan Belcher; Petrou, Vasileios I; Clarke, Oliver B et al. (2017) Structural basis for catalysis at the membrane-water interface. Biochim Biophys Acta Mol Cell Biol Lipids 1862:1368-1385 |
| Scaglione, Antonella; Montemiglio, Linda Celeste; Parisi, Giacomo et al. (2017) Subcellular localization of the five members of the human steroid 5?-reductase family. Biochim Open 4:99-106 |
| des Georges, Amédée; Clarke, Oliver B; Zalk, Ran et al. (2016) Structural Basis for Gating and Activation of RyR1. Cell 167:145-157.e17 |
| Chen, Yunting; Clarke, Oliver B; Kim, Jonathan et al. (2016) Structure of the STRA6 receptor for retinol uptake. Science 353: |
| Petrou, Vasileios I; Herrera, Carmen M; Schultz, Kathryn M et al. (2016) Structures of aminoarabinose transferase ArnT suggest a molecular basis for lipid A glycosylation. Science 351:608-12 |
| Ardiccioni, Chiara; Clarke, Oliver B; Tomasek, David et al. (2016) Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. Nat Commun 7:10175 |
| Kalathur, Ravi C; Panganiban, Marinela; Bruni, Renato (2016) High-Throughput Baculovirus Expression System for Membrane Protein Production. Methods Mol Biol 1432:187-202 |
| Bernhofer, Michael; Kloppmann, Edda; Reeb, Jonas et al. (2016) TMSEG: Novel prediction of transmembrane helices. Proteins 84:1706-1716 |
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