Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters, PepT1 and PepT2

Simon Newstead (Lead / Corresponding author), David Drew, Alexander D Cameron, Vincent LG Postis, Xiaobing Xia, Philip W Fowler, Jean C Ingram, Elisabeth P Carpenter, Mark SP Sansom, Michael J McPherson, Stephen A Baldwin (Lead / Corresponding author), So Iwata (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

213 Citations (Scopus)

Abstract

PepT1 and PepT2 are major facilitator superfamily (MFS) transporters that utilize a proton gradient to drive the uptake of di- and tri-peptides in the small intestine and kidney, respectively. They are the major routes by which we absorb dietary nitrogen and many orally administered drugs. Here, we present the crystal structure of PepTSo, a functionally similar prokaryotic homologue of the mammalian peptide transporters from Shewanella oneidensis. This structure, refined using data up to 3.6 Å resolution, reveals a ligand-bound occluded state for the MFS and provides new insights into a general transport mechanism. We have located the peptide-binding site in a central hydrophilic cavity, which occludes a bound ligand from both sides of the membrane. Residues thought to be involved in proton coupling have also been identified near the extracellular gate of the cavity. Based on these findings and associated kinetic data, we propose that PepTSo represents a sound model system for understanding mammalian peptide transport as catalysed by PepT1 and PepT2.
Original languageEnglish
Pages (from-to)417-426
Number of pages10
JournalEMBO Journal
Volume30
Issue number2
DOIs
Publication statusPublished - 3 Dec 2011

Fingerprint

Dive into the research topics of 'Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters, PepT1 and PepT2'. Together they form a unique fingerprint.

Cite this