Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transport
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2015
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| _version_ | 1797070770251235328 |
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| author | Beale, J Parker, J Samsudin, F Barrett, A Senan, A Bird, L Scott, D Owens, R Sansom, M Tucker, S Meredith, D Fowler, P Newstead, S |
| author_facet | Beale, J Parker, J Samsudin, F Barrett, A Senan, A Bird, L Scott, D Owens, R Sansom, M Tucker, S Meredith, D Fowler, P Newstead, S |
| author_sort | Beale, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:43:42Z |
| format | Journal article |
| id | oxford-uuid:5c7327d0-dd12-4499-a5fe-8fca60a5aa2a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:43:42Z |
| publishDate | 2015 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:5c7327d0-dd12-4499-a5fe-8fca60a5aa2a2022-03-26T17:28:22ZCrystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transportJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5c7327d0-dd12-4499-a5fe-8fca60a5aa2aEnglishSymplectic Elements at OxfordCell Press2015Beale, JParker, JSamsudin, FBarrett, ASenan, ABird, LScott, DOwens, RSansom, MTucker, SMeredith, DFowler, PNewstead, SMammals 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. |
| spellingShingle | Beale, J Parker, J Samsudin, F Barrett, A Senan, A Bird, L Scott, D Owens, R Sansom, M Tucker, S Meredith, D Fowler, P Newstead, S Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transport |
| title | Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transport |
| title_full | Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transport |
| title_fullStr | Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transport |
| title_full_unstemmed | Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transport |
| title_short | Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transport |
| title_sort | crystal structures of the extracellular domain from pept1 and pept2 provide novel insights into mammalian peptide transport |
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