7PMY

HsPepT2 bound to Ala-Phe in the inward facing partially occluded conformation

Summary for 7PMY

• Entry DOI: 10.2210/pdb7pmy/pdb
• EMDB information: 13544
• Descriptor: Solute carrier family 15 member 2, ALA-PHE (2 entities in total)
• Functional Keywords: hspept2, pept2, peptide transporter, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 82097.39

Authors

Killer, M.,Wald, J.,Pieprzyk, J.,Marlovits, T.C.,Loew, C. (deposition date: 2021-09-04, release date: 2021-10-20, Last modification date: 2024-07-17)

Primary citation

Killer, M.,Wald, J.,Pieprzyk, J.,Marlovits, T.C.,Low, C.
Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes.
Sci Adv, 7:eabk3259-eabk3259, 2021

PubMed Abstract: The uptake of peptides in mammals plays a crucial role in nutrition and inflammatory diseases. This process is mediated by promiscuous transporters of the solute carrier family 15, which form part of the major facilitator superfamily. Besides the uptake of short peptides, peptide transporter 1 (PepT1) is a highly abundant drug transporter in the intestine and represents a major route for oral drug delivery. PepT2 also allows renal drug reabsorption from ultrafiltration and brain-to-blood efflux of neurotoxic compounds. Here, we present cryogenic electron microscopy (cryo-EM) structures of human PepT1 and PepT2 captured in four different states throughout the transport cycle. The structures reveal the architecture of human peptide transporters and provide mechanistic insights into substrate recognition and conformational transitions during transport. This may support future drug design efforts to increase the bioavailability of different drugs in the human body.

PubMed: 34730990
DOI: 10.1126/sciadv.abk3259

Experimental method

ELECTRON MICROSCOPY (3.8 Å)