ArticleScience advances2021
Cryo-EM structure of PepT2 reveals structural basis for proton-coupled peptide and prodrug transport in mammals.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 70 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Dipeptide Transport Systems at the Interface of Peptide Metabolism and Drug Delivery in Cancer.International journal of molecular sciences · 2026Review
- Structural basis of glucosinolate recognition and transport by plant GTR1.Cell discovery · 2026Article
- Structural basis for prostaglandin and drug transport via SLCO2A1.Nature communications · 2026Article
- Applying molecular dynamics simulations to validate OCT1 substrates uncovers vitamin K1 as a high-affinity ligand.Frontiers in pharmacology · 2026Article
- Functional and Physiological Implications of Oligopeptide Transporters: Potential Targets for Pharmacological Interventions.The Journal of membrane biology · 2025Review
- Structural and functional insights of AmpG in muropeptide transport and multiple β-lactam antibiotics resistance.Nature communications · 2025Article
- Understanding, inhibiting, and engineering membrane transporters with high-throughput mutational screens.Cell chemical biology · 2025Review
- Energetics of substrate transport in proton-dependent oligopeptide transporters.Communications chemistry · 2024Article
- Structural basis for antibiotic transport and inhibition in PepT2.Nature communications · 2024Article
- Structure of the human heparan-α-glucosaminideeLife · 2024Article
- Article
- MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes.Nature cell biology · 2024Article
- Accurate model and ensemble refinement using cryo-electron microscopy maps and Bayesian inference.PLoS computational biology · 2024Article
- Structure of the human heparan-α-glucosaminidebioRxiv : the preprint server for biology · 2024Article
- Structural basis for antibiotic transport and inhibition in PepT2, the mammalian proton-coupled peptide transporter.Research square · 2024Article
- From Llama to Nanobody: A Streamlined Workflow for the Generation of Functionalised VHHs.Bio-protocol · 2024Article
- The substrate and inhibitor binding mechanism of polyspecific transporter OAT1 revealed by high-resolution cryo-EM.Nature structural & molecular biology · 2023Article
- Molecular Insights to the Structure-Interaction Relationships of Human Proton-Coupled Oligopeptide Transporters (PepTs).Pharmaceutics · 2023Review
- Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling.Nature communications · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.