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Structural basis for polyspecificity in the POT family of proton‐coupled oligopeptide transporters
Author(s) -
Lyons Joseph A,
Parker Joanne L,
Solcan Nicolae,
Brinth Alette,
Li Dianfan,
Shah Syed TA,
Caffrey Martin,
Newstead Simon
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201338403
Subject(s) - tripeptide , dipeptide , peptide , oligopeptide , transporter , symporter , chemistry , biochemistry , binding site , plasma protein binding , stereochemistry , biology , gene
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.