Journal
STRUCTURE
Volume 23, Issue 10, Pages 1889-1899Publisher
CELL PRESS
DOI: 10.1016/j.str.2015.07.016
Keywords
-
Funding
- Medical Research Council (MRC) [G0900399]
- Wellcome Trust [102890/Z/13/Z]
- MRC
- Oxford Brookes University
- MRC [MR/K018779/1, G0900399] Funding Source: UKRI
- Medical Research Council [990136, G0900399, MR/K018779/1] Funding Source: researchfish
- Wellcome Trust [102890/Z/13/Z] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available