Proton-coupled sugar transport in the prototypical major facilitator superfamily protein XylE

Nat Commun. 2014 Aug 4;5:4521. doi: 10.1038/ncomms5521.


The major facilitator superfamily (MFS) is the largest collection of structurally related membrane proteins that transport a wide array of substrates. The proton-coupled sugar transporter XylE is the first member of the MFS that has been structurally characterized in multiple transporting conformations, including both the outward and inward-facing states. Here we report the crystal structure of XylE in a new inward-facing open conformation, allowing us to visualize the rocker-switch movement of the N-domain against the C-domain during the transport cycle. Using molecular dynamics simulation, and functional transport assays, we describe the movement of XylE that facilitates sugar translocation across a lipid membrane and identify the likely candidate proton-coupling residues as the conserved Asp27 and Arg133. This study addresses the structural basis for proton-coupled substrate transport and release mechanism for the sugar porter family of proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Arginine / chemistry
  • Aspartic Acid / chemistry
  • Biological Transport
  • Escherichia coli / chemistry*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Gene Expression
  • Hydrogen Bonding
  • Lipid Bilayers / chemistry
  • Molecular Dynamics Simulation
  • Phosphatidylcholines / chemistry
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protons*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Symporters / chemistry*
  • Symporters / genetics
  • Thermodynamics
  • Xylose / chemistry*


  • Escherichia coli Proteins
  • Lipid Bilayers
  • Phosphatidylcholines
  • Protons
  • Recombinant Proteins
  • Symporters
  • xylE protein, E coli
  • Aspartic Acid
  • Arginine
  • Xylose
  • 1-palmitoyl-2-oleoylphosphatidylcholine

Associated data

  • PDB/4QIQ