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EMBO Rep. 2014 Aug;15(8):886-93. doi: 10.15252/embr.201338403. Epub 2014 Jun 10.

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

Author information

1
Schools of Medicine and Biochemistry & Immunology, Trinity College Dublin, Dublin, Ireland.
2
Department of Biochemistry, University of Oxford, Oxford, UK.
3
Schools of Medicine and Biochemistry & Immunology, Trinity College Dublin, Dublin, Ireland simon.newstead@bioch.ox.ac.uk martin.caffrey@tcd.ie.
4
Department of Biochemistry, University of Oxford, Oxford, UK simon.newstead@bioch.ox.ac.uk martin.caffrey@tcd.ie.

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.

KEYWORDS:

POT/PTR family; crystallography; major facilitator superfamily; membrane protein; peptide binding site

PMID:
24916388
PMCID:
PMC4149780
DOI:
10.15252/embr.201338403
[Indexed for MEDLINE]
Free PMC Article

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