Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian pPeptide transport

Beale, John H. and Parker, Joanne L. and Samsudin, Firdaus and Barrett, Anne L. and Senan, Anish and Bird, Louise E. and Scott, David and Owens, Raymond J. and Sansom, Mark S.P. and Tucker, Stephen J. and Meredith, David and Fowler, Philip W. and Newstead, Simon (2015) Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian pPeptide transport. Structure (London, England : 1993), 23 (10). pp. 1889-1899. ISSN 1878-4186

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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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Biosciences
Identification Number: 10.1016/j.str.2015.07.016
Depositing User: Scott, David
Date Deposited: 20 Apr 2017 10:55
Last Modified: 21 Apr 2017 15:29
URI: http://eprints.nottingham.ac.uk/id/eprint/41977

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