Authors contributed equally to study.
Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters
Article first published online: 10 JUN 2014
© 2014 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 15, Issue 8, pages 886–893, August 2014
How to Cite
EMBO Reports (2014) 15: 886–893
- Issue published online: 1 AUG 2014
- Article first published online: 10 JUN 2014
- Manuscript Accepted: 12 MAY 2014
- Manuscript Revised: 22 APR 2014
- Manuscript Received: 21 DEC 2013
- Medical Research Council (MRC) Career Development Award. Grant Number: G0900399
- Science Foundation Ireland. Grant Numbers: 07/IN.1/B1836, 12/IA/1255
- FP7 COST Action. Grant Number: CM0902
- National Institutes of Health. Grant Numbers: P50GM073210, U54GM094599
- Danish Council for Independent Research in Natural Sciences
- major facilitator superfamily;
- membrane protein;
- peptide binding site;
- POT/PTR family
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.
Mammalian members of the POT family transport both di- and tripeptides. This study shows that a bacterial member of this family is able to recognize di- and tripeptides in different orientations, explaining this remarkable ligand promiscuity.
- Crystal structures of a POT transporter bound by di- and tripeptides.
- Structural and biochemical data support alternative binding modes for these peptides.