title: Proton-coupled sugar transport in the prototypical major facilitator superfamily protein XylE.
abstract: 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.
authors.affiliation: 1] Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA [2].
authors.forename: Goragot
authors.initials: G
authors.lastname: Wisedchaisri
authors.affiliation: 1] Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA [2].
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Park
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Iadanza
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA.
authors.forename: Hongjin
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA.
authors.forename: Tamir
authors.initials: T
authors.lastname: Gonen
mesh_terms: D001120:Arginine / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D001692:Biological Transport; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D015870:Gene Expression; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D027981:Symporters / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics; D014994:Xylose / Q000737:chemistry*
chemical_list: D029968:Escherichia coli Proteins; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D011522:Protons; D011994:Recombinant Proteins; D027981:Symporters; C033903:xylE protein, E coli; D001224:Aspartic Acid; D001120:Arginine; D014994:Xylose; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
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