Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.str.2015.07.016

Type

Journal article

Journal

Structure

Publication Date

06/10/2015

Volume

23

Pages

1889 - 1899

Keywords

Amino Acid Sequence, Animals, Binding Sites, Crystallography, X-Ray, Escherichia coli, Gene Expression, Humans, Kinetics, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Oligopeptides, Peptide Transporter 1, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Transport, Rats, Recombinant Proteins, Symporters, Trypsin