RGD Reference Report - Cryo-EM structure of PepT2 reveals structural basis for proton-coupled peptide and prodrug transport in mammals. - Rat Genome Database

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Cryo-EM structure of PepT2 reveals structural basis for proton-coupled peptide and prodrug transport in mammals.

Authors: Parker, Joanne L  Deme, Justin C  Wu, Zhiyi  Kuteyi, Gabriel  Huo, Jiandong  Owens, Raymond J  Biggin, Philip C  Lea, Susan M  Newstead, Simon 
Citation: Parker JL, etal., Sci Adv. 2021 Aug 25;7(35):eabh3355. doi: 10.1126/sciadv.abh3355. Print 2021 Aug.
RGD ID: 329845499
Pubmed: PMID:34433568   (View Abstract at PubMed)
PMCID: PMC8386928   (View Article at PubMed Central)
DOI: DOI:10.1126/sciadv.abh3355   (Journal Full-text)

The SLC15 family of proton-coupled solute carriers PepT1 and PepT2 play a central role in human physiology as the principal route for acquiring and retaining dietary nitrogen. A remarkable feature of the SLC15 family is their extreme substrate promiscuity, which has enabled the targeting of these transporters for the improvement of oral bioavailability for several prodrug molecules. Although recent structural and biochemical studies on bacterial homologs have identified conserved sites of proton and peptide binding, the mechanism of peptide capture and ligand promiscuity remains unclear for mammalian family members. Here, we present the cryo-electron microscopy structure of the outward open conformation of the rat peptide transporter PepT2 in complex with an inhibitory nanobody. Our structure, combined with molecular dynamics simulations and biochemical and cell-based assays, establishes a framework for understanding peptide and prodrug recognition within this pharmaceutically important transporter family.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc15a2Ratdipeptide import across plasma membrane involved_inIDA PMID:34433568UniProt 
Slc15a2Rattripeptide import across plasma membrane involved_inIDA PMID:34433568UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc15a2Ratdipeptide transmembrane transporter activity enablesIDA PMID:34433568UniProt 
Slc15a2Ratpeptide:proton symporter activity enablesIDA PMID:34433568UniProt 
Slc15a2Rattripeptide transmembrane transporter activity enablesIDA PMID:34433568UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Slc15a2  (solute carrier family 15 member 2)


Additional Information