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Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters

DOI: 10.15252/embr.201338403 DOI Help
PMID: 24916388 PMID Help

Authors: J. A. Lyons (Schools of Medicine and Biochemistry & Immunology, Trinity College Dublin, Ireland) , Joanne Parker (University of Oxford) , Nicolae Solcan (University of Oxford) , Alette Brinth (Trinity College, Dublin) , Dianfan Li (Trinity College, Dublin) , S. T. Shah (Schools of Medicine and Biochemistry & Immunology, Trinity College Dublin, Ireland) , Martin Caffrey (Trinity College, Dublin) , S. Newstead (Department of Biochemistry, University of Oxford, UK)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Embo Reports , VOL 15 (8) , PAGES 886 - 893

State: Published (Approved)
Published: August 2014
Diamond Proposal Number(s): 8224

Open Access Open Access

Abstract: An enigma in the field of peptide transport is the structural basis for ligand promiscuity, as exemplified by PepT1, the mammalian plasma membrane peptide transporter. Here, we present crystal structures of di- and tripeptide-bound complexes of a bacterial homologue of PepT1, which reveal at least two mechanisms for peptide recognition that operate within a single, centrally located binding site. The dipeptide was orientated laterally in the binding site, whereas the tripeptide revealed an alternative vertical binding mode. The co-crystal structures combined with functional studies reveal that biochemically distinct peptide-binding sites likely operate within the POT/PTR family of proton-coupled symporters and suggest that transport promiscuity has arisen in part through the ability of the binding site to accommodate peptides in multiple orientations for transport

Subject Areas: Biology and Bio-materials

Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: APS