title: Molecular insights into proton coupled peptide transport in the PTR family of oligopeptide transporters.
abstract: BACKGROUND
  Cellular uptake of small peptides is an important physiological process mediated by the PTR family of proton-coupled peptide transporters. In bacteria peptides can be used as a source of amino acids and nitrogen. Similarly in humans peptide transport is the principle route for the uptake and retention of dietary protein in the form of short di- and tri-peptides for cellular metabolism.
  
  
  OBJECTIVE
  Recent crystal structures of bacterial PTR family transporters, combined with biochemical studies of transport have revealed key molecular details underpinning ligand promiscuity and the mechanism of proton-coupled transport within the family.
  
  
  CONCLUSIONS
  Pairs of salt bridge interactions between transmembrane helices work in tandem to orchestrate alternating access transport within the PTR family. Key roles for residues conserved between bacterial and eukaryotic homologues suggest a conserved mechanism of peptide recognition and transport that in some cases has been subtly modified in individual species.
  
  
  CONCLUSIONS
  Physiological studies on PepT1 and PepT2, the mammalian members of this family, have identified these transporters as being responsible for the uptake of many pharmaceutically important drug molecules, including antibiotics and antiviral medications and demonstrated their promiscuity can be used for improving the oral bioavailability of poorly absorbed compounds. The insights gained from recent structural studies combined with previous physiological and biochemical analyses are rapidly advancing our understanding of this medically important transporter superfamily. This article is part of a Special Issue entitled Structural biochemistry and biophysics of membrane proteins.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Newstead
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism* / Q000493:pharmacokinetics*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D009842:Oligopeptides
keywords: Drug transport; Major facilitator superfamily; PTR/NRT1/POT family; Peptide transport