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Structure. 2015 Feb 3;23(2):290-301. doi: 10.1016/j.str.2014.12.012.

Gating topology of the proton-coupled oligopeptide symporters.

Author information

1
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: philip.fowler@bioch.ox.ac.uk.
2
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
3
Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, Frankfurt am Main, Germany.
4
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
5
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: simon.newstead@bioch.ox.ac.uk.

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.

PMID:
25651061
PMCID:
PMC4321885
DOI:
10.1016/j.str.2014.12.012
[Indexed for MEDLINE]
Free PMC Article

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