Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transport
| Autor: | Beale, John H., Parker, Joanne L., Meredith, David, Fowler, Philip W., Newstead, Simon, Samsudin, Firdaus, Barrett, Anne L., Senan, Anish, Bird, Louise E., Scott, David, Owens, Raymond J., Sansom, Mark S. P., Tucker, Stephen J. |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Molecular Sequence Data Gene Expression Crystallography X-Ray Peptide Transporter 1 Protein Structure Secondary Article Mice Structural Biology ddc:570 Escherichia coli Animals Humans Trypsin Amino Acid Sequence Molecular Biology Binding Sites Symporters Recombinant Proteins Protein Structure Tertiary Rats Kinetics Protein Transport Mutation Oligopeptides Protein Binding |
| Zdroj: | Structure(London, England:1993) Structure 23(10), 1889-1899 (2015). doi:10.1016/j.str.2015.07.016 |
| ISSN: | 0969-2126 1878-4186 |
| DOI: | 10.1016/j.str.2015.07.016 |
| Popis: | Summary 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. Graphical Abstract Highlights • Crystal structure of the extracellular domains of PepT1 and PepT2 • Modular architecture for a mammalian MFS transporter • Extracellular domains contain immunoglobulin-like fold and interact with trypsin The crystal structure of PepT1 and PepT2 reported by Beale et al. reveals two immunoglobulin-like domains connected in tandem inserted within the canonical major facilitator superfamily fold. Biophysical analyses reveal a specific interaction with trypsin, suggesting a role in clustering proteolytic activity to the site of peptide uptake across the membrane. |
| Databáze: | OpenAIRE |
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