title: Structural insights into substrate recognition in proton-dependent oligopeptide transporters.
abstract: Short-chain peptides are transported across membranes through promiscuous proton-dependent oligopeptide transporters (POTs)--a subfamily of the major facilitator superfamily (MFS). The human POTs, PEPT1 and PEPT2, are also involved in the absorption of various drugs in the gut as well as transport to target cells. Here, we present a structure of an oligomeric POT transporter from Shewanella oneidensis (PepTSo2), which was crystallized in the inward open conformation in complex with the peptidomimetic alafosfalin. All ligand-binding residues are highly conserved and the structural insights presented here are therefore likely to also apply to human POTs.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors.forename: Fatma
authors.initials: F
authors.lastname: Guettou
authors.forename: Esben M
authors.initials: EM
authors.lastname: Quistgaard
authors.forename: Lionel
authors.initials: L
authors.lastname: Trésaugues
authors.forename: Per
authors.initials: P
authors.lastname: Moberg
authors.forename: Caroline
authors.initials: C
authors.lastname: Jegerschöld
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Agnes Jin Oi
authors.initials: AJ
authors.lastname: Jong
authors.forename: Pär
authors.initials: P
authors.lastname: Nordlund
authors.forename: Christian
authors.initials: C
authors.lastname: Löw
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D020592:Shewanella / Q000737:chemistry* / Q000378:metabolism; D027981:Symporters / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D027981:Symporters; C006437:alafosfalin; D000409:Alanine