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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.

Original publication

DOI

10.1016/j.str.2014.12.012

Type

Journal article

Journal

Structure

Publication Date

03/02/2015

Volume

23

Pages

290 - 301

Keywords

Bacteria, Biological Transport, Active, Crystallography, Electron Spin Resonance Spectroscopy, Models, Molecular, Molecular Dynamics Simulation, Protein Conformation, Spectrum Analysis, Symporters