Gating topology of the proton-coupled oligopeptide symporters.

Autor: Fowler PW; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: philip.fowler@bioch.ox.ac.uk., Orwick-Rydmark M; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Radestock S; Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, Frankfurt am Main, Germany., Solcan N; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Dijkman PM; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Lyons JA; School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland., Kwok J; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Caffrey M; School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland., Watts A; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK., Forrest LR; Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, Frankfurt am Main, Germany., Newstead S; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: simon.newstead@bioch.ox.ac.uk.
Jazyk: angličtina
Zdroj: Structure (London, England : 1993) [Structure] 2015 Feb 03; Vol. 23 (2), pp. 290-301.
DOI: 10.1016/j.str.2014.12.012
Abstrakt: 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.
(Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE