This is a competitive renewal application for a grant that supports the Biotechnology Resource for NMR Molecular Imaging of Proteins at the University of California, San Diego. The BTRC develops and applies NMR spectroscopy for the study of proteins in biological supermolecular structures, such as virus particles and membranes. Successful applications of nuclear magnetic resonance (NMR) spectroscopy to proteins have been largely limited to the same class of soluble, globular proteins that are amenable to X-ray crystallography. However, methods that work well with globular proteins typically work poorly with membrane proteins in their native crystalline phospholipid bilayer environment. It is this technology gap that we seek to fill. The BTRC is highly focused on advancing the technology for high-resolution solid-state NMR spectroscopy so that it can be used in laboratories throughout the World to determine the structure of membrane proteins under near-native conditions. It is this unique technology that we will make available to the Nation's biomedical research community through our Collaborative (CP) and Service (SP) research projects. Membrane proteins are important targets for structural studies because they represent about one-third of the proteins expressed from the genomes of all organisms and have many unique roles, including as drug receptors where they have their greatest biomedical roles. Primary targets for the research at the BTRC include G-protein coupled receptors (GPCRs), which are the largest class of membrane proteins and of drug receptors. Information about their structures will help guide the development of new drugs for a wide range of diseases, ranging from cancer to mental illness.

Public Health Relevance

The technology developed at the BTRC will accelerate the development of drugs against a wide range of diseases. The information gained in the studies carried out with this technology will disclose the details of how drugs bind to their molecular partners, which are the actual players the affect diseases. This information will help in the discovery of new drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Biotechnology Resource Grants (P41)
Project #
5P41EB002031-24
Application #
9271190
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Atanasijevic, Tatjana
Project Start
1994-04-10
Project End
2019-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
24
Fiscal Year
2017
Total Cost
Indirect Cost
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
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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
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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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