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id="title" class="nomar"Membrane Protein Structures by Solution NMR

The MPSbyNMR center is a PSI membrane protein structure determination center, and consists of investigators from  Harvard Medical School, Vanderbilt University, Frankfurt University, Los Alamos National Laboratory, and FB Reagents.

Member Institutions

  • Harvard Medical School
    James Chou
    Gerhard Wagner
    Piotr Sliz
  • Dana-Farber Cancer Institute, Harvard Medical School
    William Shih
  • Vanderbilt University
    Charles Sanders
  • Frankfurt University
    Volker Dotsch
  • Bioscience division of Los Alamos National Laboratory
    Alexander Kolgin
  • FB Reagents
    Vlado Gelev

Contact Information

James Chou
chou@cmcd.hms.harvard.edu

Research Description

A Protein Structure Initiative (PSI) Center that aims to develop an efficient solution NMR pipeline for solving membrane protein (MP) structures. To drive technology development and to test the proposed pipeline, we have selected 10 MP targets for which the structures are not known, including membrane-embedded transporters, enzymes, and receptors. These targets are polytopic helical MPs with 3-7 transmembrane helices and with sizes from 18 – 43 kDa. The Center will develop technologies that will have immediate and practical impact on structure determination. They include (1) cell-free expression platforms for production of MPs and for screening for NMR-feasible MP targets; (2) new detergents, bicelles and MP refolding methods; (3) non-uniform sampled high resolution 4D NOESYs; (4) new strategies for selective isotope labeling of methyl groups for acquiring long-range NOEs; (5) novel reagent for site-directed paramagnetic tagging and universal DNA-nanotube alignment media for RDC measurements; and (6) RDC-based molecular fragment replacement and structure calculation protocols. Although the phrase “high-throughput” does not yet apply to MP in any technological context, we aim to establish a NMR tool package within the proposed funding period that has the capacity for systematic production of MP structures.

Key Publications
  1. Schnell JR, Chou JJ.
    Structure and mechanism of the M2 proton channel of influenza A virus,

    Nature.,2008 Jan 31;451(7178):591-5. (PubMed ID: 18235503).
  2. Call ME, Wucherpfennig KW, Chou JJ
    The structural basis for intramembrane assembly of an activating immunoreceptor complex.

    Nat Immunol.,2010 Oct 3. (PubMed ID: 20890284).
  3. Hiller S, Garces RG, Malia TJ, Orekhov VY, Colombini M, Wagner G.
    Solution structure of the integral human membrane protein VDAC-1 in detergent micelles.

    Science.,2008 Aug 29;321(5893):1206-10. (PubMed ID: 18755977).
  4. Van Horn WD, Kim HJ, Ellis CD, Hadziselimovic A, Sulistijo ES, Karra MD, Tian C, Sönnichsen FD, Sanders CR
    Solution nuclear magnetic resonance structure of membrane-integral diacylglycerol kinase.

    Science.,2009 Jun 26;324(5935):1726-9. (PubMed ID: 19556511).

Structures, Targets, Publications and Technologies

MPSbyNMR Structures in RCSB PDB
MPSbyNMR Targets in TargetTrack
MPSbyNMR SBKB Publications Page
MPSbyNMR SBKB Technology Portal Page

Relevant Links

Center profile in Technology Portal

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health