John H. Beale
Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian pPeptide transport
Beale, John H.; Parker, Joanne L.; Samsudin, Firdaus; Barrett, Anne L.; Senan, Anish; Bird, Louise E.; Scott, David; Owens, Raymond J.; Sansom, Mark S.P.; Tucker, Stephen J.; Meredith, David; Fowler, Philip W.; Newstead, Simon
Authors
Joanne L. Parker
Firdaus Samsudin
Anne L. Barrett
Anish Senan
Louise E. Bird
DAVID SCOTT DAVID.SCOTT@NOTTINGHAM.AC.UK
Associate Professor & Reader in Physical Biochemistry
Raymond J. Owens
Mark S.P. Sansom
Stephen J. Tucker
David Meredith
Philip W. Fowler
Simon Newstead
Abstract
Mammals obtain nitrogen via the uptake of di- and tri-peptides in the gastrointestinal tract through the action of PepT1 and PepT2, which are members of the POT family of proton-coupled oligopeptide transporters. PepT1 and PepT2 also play an important role in drug transport in the human body. Recent crystal structures of bacterial homologs revealed a conserved peptide-binding site and mechanism of transport. However, a key structural difference exists between bacterial and mammalian homologs with only the latter containing a large extracellular domain, the function of which is currently unknown. Here, we present the crystal structure of the extracellular domain from both PepT1 and PepT2 that reveal two immunoglobulin-like folds connected in tandem, providing structural insight into mammalian peptide transport. Functional and biophysical studies demonstrate that these domains interact with the intestinal protease trypsin, suggesting a role in clustering proteolytic activity to the site of peptide transport in eukaryotic cells.
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 28, 2015 |
Online Publication Date | Aug 27, 2015 |
Publication Date | Oct 6, 2015 |
Deposit Date | Apr 20, 2017 |
Publicly Available Date | Apr 20, 2017 |
Journal | Structure (London, England : 1993) |
Print ISSN | 0969-2126 |
Electronic ISSN | 1878-4186 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 23 |
Issue | 10 |
DOI | https://doi.org/10.1016/j.str.2015.07.016 |
Public URL | https://nottingham-repository.worktribe.com/output/764469 |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S0969212615003226 |
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Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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