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 thei 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 #
2P41EB002031-21
Application #
8746982
Study Section
Special Emphasis Panel (ZEB1-OSR-E (M3))
Program Officer
Liu, Christina
Project Start
1994-04-10
Project End
2019-05-31
Budget Start
2014-06-15
Budget End
2015-05-31
Support Year
21
Fiscal Year
2014
Total Cost
$1,679,177
Indirect Cost
$398,261
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
Gong, Xiao-Min; Ding, Yi; Yu, Jinghua et al. (2015) Structure of the Na,K-ATPase regulatory protein FXYD2b in micelles: implications for membrane-water interfacial arginines. Biochim Biophys Acta 1848:299-306
Das, Bibhuti B; Park, Sang Ho; Opella, Stanley J (2015) Membrane protein structure from rotational diffusion. Biochim Biophys Acta 1848:229-45
Park, Sang Ho; Wang, Vivian S; Radoicic, Jasmina et al. (2015) Paramagnetic relaxation enhancement of membrane proteins by incorporation of the metal-chelating unnatural amino acid 2-amino-3-(8-hydroxyquinolin-3-yl)propanoic acid (HQA). J Biomol NMR 61:185-96
Perrin Jr, B Scott; Tian, Ye; Fu, Riqiang et al. (2014) High-resolution structures and orientations of antimicrobial peptides piscidin 1 and piscidin 3 in fluid bilayers reveal tilting, kinking, and bilayer immersion. J Am Chem Soc 136:3491-504
Lin, Eugene C; Opella, Stanley J (2014) Covariance spectroscopy in high-resolution multi-dimensional solid-state NMR. J Magn Reson 239:57-60
Tian, Ye; Schwieters, Charles D; Opella, Stanley J et al. (2014) A practical implicit solvent potential for NMR structure calculation. J Magn Reson 243:54-64
Tian, Ye; Lu, George J; Marassi, Francesca M et al. (2014) Structure of the membrane protein MerF, a bacterial mercury transporter, improved by the inclusion of chemical shift anisotropy constraints. J Biomol NMR 60:67-71
Lu, George J; Opella, Stanley J (2014) Mechanism of dilute-spin-exchange in solid-state NMR. J Chem Phys 140:124201
Wu, Chin H; De Angelis, Anna A; Opella, Stanley J (2014) Magic angle Lee-Goldburg frequency offset irradiation improves the efficiency and selectivity of SPECIFIC-CP in triple-resonance MAS solid-state NMR. J Magn Reson 246:1-3
Radoicic, Jasmina; Lu, George J; Opella, Stanley J (2014) NMR structures of membrane proteins in phospholipid bilayers. Q Rev Biophys 47:249-83

Showing the most recent 10 out of 112 publications