| First Author | Beale JH | Year | 2015 |
| Journal | Structure | Volume | 23 |
| Issue | 10 | Pages | 1889-1899 |
| PubMed ID | 26320580 | Mgi Jnum | J:292534 |
| Mgi Id | MGI:6450380 | Doi | 10.1016/j.str.2015.07.016 |
| Citation | Beale JH, et al. (2015) Crystal Structures of the Extracellular Domain from PepT1 and PepT2 Provide Novel Insights into Mammalian Peptide Transport. Structure 23(10):1889-1899 |
| abstractText | 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. |
