Fine Sampling of Sequence Space for Membrane Protein Structural Biology |
| |
| Affiliation: | 1. Center on Membrane Protein Production and Analysis (COMPPÅ), New York Structural Biology Center (NYSBC), New York, NY 10027, USA;2. Rockefeller University, New York, NY 10065, USA;3. Schrödinger, Inc., New York, NY 10036, USA;4. Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA;5. Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA;1. Department of Biochemistry and Molecular Biophysics, Box 8231, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States;2. Department of Physics, Washington University in St. Louis, St. Louis, MO 63130, United States;1. University of Toronto, Department of Molecular Genetics, Donnelly Centre, 160 College Street, Toronto, ON M5S 3E1, Canada;2. Bristol Myers Squibb Co., Discovery Biotherapeutics, 4242 Campus Point Court Suite 700, San Diego, CA 92121, USA;3. The University of Chicago, Department of Biochemistry and Molecular Biology, 929 East 57th Street, Chicago, IL 60637, USA;4. University of California San Francisco, Department of Pharmaceutical Chemistry, 505 Parnassus Ave, San Francisco, CA 94143, USA;1. Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK;2. Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia;3. ARC Centre for Fragment-Based Design, Monash University, Parkville, Victoria 3052, Australia;1. New York Structural Biology Center, New York, NY, USA;2. Department of Biomedical Sciences, University at Albany, Albany, NY, USA;3. Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY, USA;4. Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway;5. Department of Biosciences, University of Oslo, Oslo, Norway;1. Department of Chemical and Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel;2. Department of Biomolecular Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel;3. Department of Cell Research and Immunology, The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel;4. Department of Chemistry, University of California, Davis, CA 95616, USA |
| |
| Abstract: | We describe an enhancement of traditional genomics-based approaches to improve the success of structure determination of membrane proteins. Following a broad screen of sequence space to identify initial expression-positive targets, we employ a second step to select orthologs with closely related sequences to these hits. We demonstrate that a greater percentage of these latter targets express well and are stable in detergent, increasing the likelihood of identifying candidates that will ultimately yield structural information. |
| |
| Keywords: | structural biology structural genomics integral membrane proteins protein expression protein purification high throughput biology NYCOMPS" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" New York Consortium on Membrane Protein Structure COMPPÅ" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" Center on Membrane Protein Production and Analysis SEC" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" size exclusion chromatography DDM" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" n-Dodecyl-β-D-Maltopyranoside DM" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" n-decyl-β-D-maltopyranoside β-OG" },{" #name" :" keyword" ," $" :{" id" :" k0100" }," $$" :[{" #name" :" text" ," _" :" n-octyl-β-D-glucopyranoside LDAO" },{" #name" :" keyword" ," $" :{" id" :" k0110" }," $$" :[{" #name" :" text" ," _" :" n-dodecyl-N,N-dimethylamine-N-oxide TEV" },{" #name" :" keyword" ," $" :{" id" :" k0120" }," $$" :[{" #name" :" text" ," _" :" tobacco etch virus IPTG" },{" #name" :" keyword" ," $" :{" id" :" k0130" }," $$" :[{" #name" :" text" ," _" :" Isopropyl β-d-1-thiogalactopyranoside AEBSF" },{" #name" :" keyword" ," $" :{" id" :" k0140" }," $$" :[{" #name" :" text" ," _" :" 4-benzenesulfonyl fluoride hydrochloride nickel nitrilotriacetic acid HEPES" },{" #name" :" keyword" ," $" :{" id" :" k0160" }," $$" :[{" #name" :" text" ," _" :" 2-[4-(2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acid TCEP-HCl" },{" #name" :" keyword" ," $" :{" id" :" k0170" }," $$" :[{" #name" :" text" ," _" :" Tris (2-Carboxyethyl) phosphine Hydrochloride |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
