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Gating topology of the proton-coupled oligopeptide symporters

DOI: 10.1016/j.str.2014.12.012 DOI Help
PMID: 25651061 PMID Help

Authors: Philip W. Fowler (University of Oxford) , Marcella Orwick-Rydmark (University of Oxford) , Sebastian Radestock (Max Planck Institute of Biophysics) , Nicolae Solcan (University of Oxford) , Patricia M. Dijkman (University of Oxford) , Joseph Lyons (Trinity College Dublin) , Jane Kwok (University of Oxford) , Martin Caffrey (Trinity College, Dublin) , Anthony Watts (University of Oxford) , Lucy R. Forrest (Max Planck Institute of Biophysics) , Simon Newstead (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 23 (2) , PAGES 290 - 301

State: Published (Approved)
Published: February 2015
Diamond Proposal Number(s): 8224 , 8518

Open Access Open Access

Abstract: Proton-coupled oligopeptide transporters belong to the major facilitator superfamily (MFS) of membrane transporters. Recent crystal structures suggest the MFS fold facilitates transport through rearrangement of their two six-helix bundles around a central ligand binding site; how this is achieved, however, is poorly understood. Using modeling, molecular dynamics, crystallography, functional assays, and site-directed spin labeling combined with double electron-electron resonance (DEER) spectroscopy, we present a detailed study of the transport dynamics of two bacterial oligopeptide transporters, PepTSo and PepTSt. Our results identify several salt bridges that stabilize outward-facing conformations and we show that, for all the current structures of MFS transporters, the first two helices of each of the four inverted-topology repeat units form half of either the periplasmic or cytoplasmic gate and that these function cooperatively in a scissor-like motion to control access to the peptide binding site during transport.

Journal Keywords: Lipid Cubic Phase; Peptso

Subject Areas: Biology and Bio-materials

Instruments: I24-Microfocus Macromolecular Crystallography

Added On: 30/03/2015 16:10

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)