Abstract

This is the competitive renewal application for grant P41EB002031-11. It requests support to continue the development and application of NMR spectroscopy for structure determination of proteins in supramolecular assemblies. Of particular interest, are applications to membrane proteins with one or a few trans-membrane helices that constitute one-third of the expressed proteins in a genome; G-protein coupled receptors (GPCRs) with seven trans-membrane helices that are the major class of drug receptors; and peptide sequences incorporated and displayed on the surface of filamentous bacteriophages that are leads for vaccine and drug development. The feasibility of determining the three-dimensional structures of proteins in supramolecular assemblies by solid-state NMR spectroscopy has been demonstrated during the current funding period. High throughput structure determination and applications to larger membrane proteins require further development of the instrumentation and experimental methods for high-field solid-state NMR spectroscopy. In particular, the Resource is poised to capitalize on the opportunities presented by the 900 MHz magnet, and its new location at the University of California, San Diego in the center of one of the highest concentration of biomedical research activity in the Nation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Biotechnology Resource Grants (P41)
Project #
5P41EB002031-12
Application #
6878571
Study Section
Special Emphasis Panel (ZRG1-BBCA (40))
Program Officer
Mclaughlin, Alan Charles
Project Start
1994-04-10
Project End
2009-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
12
Fiscal Year
2005
Total Cost
$683,564
Indirect Cost

  Institution

Name
University of California San Diego
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

McKay, Matthew J; Martfeld, Ashley N; De Angelis, Anna A et al. (2018) Control of Transmembrane Helix Dynamics by Interfacial Tryptophan Residues. Biophys J 114:2617-2629
Radoicic, Jasmina; Park, Sang Ho; Opella, Stanley J (2018) Macrodiscs Comprising SMALPs for Oriented Sample Solid-State NMR Spectroscopy of Membrane Proteins. Biophys J 115:22-25
Dutta, Samit Kumar; Yao, Yong; Marassi, Francesca M (2017) Structural Insights into the Yersinia pestis Outer Membrane Protein Ail in Lipid Bilayers. J Phys Chem B 121:7561-7570
Berkamp, Sabrina; Park, Sang Ho; De Angelis, Anna A et al. (2017) Structure of monomeric Interleukin-8 and its interactions with the N-terminal Binding Site-I of CXCR1 by solution NMR spectroscopy. J Biomol NMR 69:111-121
Tian, Ye; Schwieters, Charles D; Opella, Stanley J et al. (2017) High quality NMR structures: a new force field with implicit water and membrane solvation for Xplor-NIH. J Biomol NMR 67:35-49
Opella, Stanley J; Marassi, Francesca M (2017) Applications of NMR to membrane proteins. Arch Biochem Biophys 628:92-101
Park, Sang Ho; Berkamp, Sabrina; Radoicic, Jasmina et al. (2017) Interaction of Monomeric Interleukin-8 with CXCR1 Mapped by Proton-Detected Fast MAS Solid-State NMR. Biophys J 113:2695-2705
Yao, Yong; Dutta, Samit Kumar; Park, Sang Ho et al. (2017) High resolution solid-state NMR spectroscopy of the Yersinia pestis outer membrane protein Ail in lipid membranes. J Biomol NMR 67:179-190
Yao, Yong; Nisan, Danielle; Fujimoto, Lynn M et al. (2016) Characterization of the membrane-inserted C-terminus of cytoprotective BCL-XL. Protein Expr Purif 122:56-63
Das, Bibhuti B; Opella, Stanley J (2016) Simultaneous cross polarization to (13)C and (15)N with (1)H detection at 60kHz MAS solid-state NMR. J Magn Reson 262:20-26

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