ArticleProceedings of the National Academy of Sciences of the United States of America2017
Proton movement and coupling in the POT family of peptide transporters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 99 citations in OpenAlex.
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- MARC, a novel modular chimeric antigen receptor, improves T cell-based cancer immunotherapies by preventing early T cell exhaustion and enhancing persistence.Journal for immunotherapy of cancer · 2025Article
- Plant hormones and membrane transporters: integrating nutrient uptake, ion homeostasis, and stress responses through hormonal cross-talk.Frontiers in plant science · 2025Review
- Energetics of substrate transport in proton-dependent oligopeptide transporters.Communications chemistry · 2024Article
- Transport mechanism of DgoT, a bacterial homolog of SLC17 organic anion transporters.The EMBO journal · 2024Article
- Structural basis for antibiotic transport and inhibition in PepT2.Nature communications · 2024Article
- Article
- Molecular basis for pH sensing in the KDEL trafficking receptor.Structure (London, England : 1993) · 2024Article
- Structural basis for antibiotic transport and inhibition in PepT2, the mammalian proton-coupled peptide transporter.Research square · 2024Article
- Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Molecular Insights to the Structure-Interaction Relationships of Human Proton-Coupled Oligopeptide Transporters (PepTs).Pharmaceutics · 2023Review
- Molecular basis of TASL recruitment by the peptide/histidine transporter 1, PHT1.Nature communications · 2023Article
- Structural basis of purine nucleotide inhibition of human uncoupling protein 1.Science advances · 2023Article
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- Bactericidal Properties of Proline-RichLife (Basel, Switzerland) · 2022Article
- Generalized Transition State Theory Treatment of Water-Assisted Proton Transport Processes in Proteins.The journal of physical chemistry. B · 2022Article
- Biology of Peptide Transporter 2 in Mammals: New Insights into Its Function, Structure and Regulation.Cells · 2022Review
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
POT transporters represent an evolutionarily well-conserved family of proton-coupled transport systems in biology. An unusual feature of the family is their ability to couple the transport of chemically diverse ligands to an inwardly directed proton electrochemical gradient. For example, in mammals, fungi, and bacteria they are predominantly peptide transporters, whereas in plants the family has diverged to recognize nitrate, plant defense compounds, and hormones. Although recent structural and biochemical studies have identified conserved sites of proton binding, the mechanism through which transport is coupled to proton movement remains enigmatic. Here we show that different POT transporters operate through distinct proton-coupled mechanisms through changes in the extracellular gate. A high-resolution crystal structure reveals the presence of ordered water molecules within the peptide binding site. Multiscale molecular dynamics simulations confirm proton transport occurs through these waters via Grotthuss shuttling and reveal that proton binding to the extracellular side of the transporter facilitates a reorientation from an inward- to outward-facing state. Together these results demonstrate that within the POT family multiple mechanisms of proton coupling have likely evolved in conjunction with variation of the extracellular gate.
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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.