Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters, PepT1 and PepT2
Open Access
- 18 January 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 30 (2), 417-426
- https://doi.org/10.1038/emboj.2010.309
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 PepT(So), a functionally similar prokaryotic homologue of the mammalian peptide transporters from Shewanella oneidensis. This structure, refined using data up to 3.6 angstrom 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 PepT(So) represents a sound model system for understanding mammalian peptide transport as catalysed by PepT1 and PepT2. The EMBO Journal (2011) 30, 417-426. doi:10.1038/emboj.2010.309; Published online 3 December 2010This publication has 65 references indexed in Scilit:
- Structural perspectives on secondary active transportersTrends in Pharmacological Sciences, 2010
- The transmembrane tyrosines Y56, Y91 and Y167 play important roles in determining the affinity and transport rate of the rabbit proton-coupled peptide transporter PepT1The International Journal of Biochemistry & Cell Biology, 2009
- Mutagenesis and Cysteine Scanning of Transmembrane Domain 10 of the Human Dipeptide TransporterPharmaceutical Research, 2009
- Clogging the Periplasmic Pathway in LacYBiochemistry, 2009
- Opening and closing of the periplasmic gate in lactose permeaseProceedings of the National Academy of Sciences of the United States of America, 2008
- Toward the structural genomics of complexes: Crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosisProceedings of the National Academy of Sciences of the United States of America, 2006
- Sequence Alignment and Homology Threading Reveals Prokaryotic and Eukaryotic Proteins Similar to Lactose PermeaseJournal of Molecular Biology, 2006
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997
- VMD: Visual molecular dynamicsJournal of Molecular Graphics, 1996
- NMRPipe: A multidimensional spectral processing system based on UNIX pipesJournal of Biomolecular NMR, 1995