Journal: Sci Adv / Year: 2021 Title: Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes. Authors: Maxime Killer / Jiri Wald / Joanna Pieprzyk / Thomas C Marlovits / Christian Löw / 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 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.
History
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Sep 3, 2021
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Header (metadata) release
Oct 20, 2021
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Map release
Oct 20, 2021
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Update
Jul 17, 2024
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Current status
Jul 17, 2024
Processing site: PDBe / Status: Released
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