title: Thermodynamic evidence for a dual transport mechanism in a POT peptide transporter.
abstract: Peptide transport plays an important role in cellular homeostasis as a key route for nitrogen acquisition in mammalian cells. PepT1 and PepT2, the mammalian proton coupled peptide transporters (POTs), function to assimilate and retain diet-derived peptides and play important roles in drug pharmacokinetics. A key characteristic of the POT family is the mechanism of peptide selectivity, with members able to recognise and transport >8000 different peptides. In this study, we present thermodynamic evidence that in the bacterial POT family transporter PepTSt, from Streptococcus thermophilus, at least two alternative transport mechanisms operate to move peptides into the cell. Whilst tri-peptides are transported with a proton:peptide stoichiometry of 3:1, di-peptides are co-transported with either 4 or 5 protons. This is the first thermodynamic study of proton:peptide stoichiometry in the POT family and reveals that secondary active transporters can evolve different coupling mechanisms to accommodate and transport chemically and physically diverse ligands across the membrane.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Parker
authors.affiliation: Membrane Transport Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Mindell
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Newstead
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D021381:Protein Transport; D048249:Streptococcus thermophilus / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C043912:peptide permease
keywords: POT family; biochemistry; major facilitator superfamily; membrane transport; none; peptide transport; thermodynamics