ArticlePharmaceutical research2007
A charge pair interaction between Arg282 in transmembrane segment 7 and Asp341 in transmembrane segment 8 of hPepT1.
Article in Pharmaceutical research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- In silico directed evolution of humanized peptide transporters via computational epistatic rescue.Molecular diversity · 2026Article
- Article
- PepT1 mRNA expression levels in sea bream (Sparus aurata) fed different plant protein sources.SpringerPlus · 2013Article
- Functional and structural determinants of reverse operation in the pH-dependent oligopeptide transporter PepT1.Cellular and molecular life sciences : CMLS · 2011Article
- Residues R282 and D341 act as electrostatic gates in the proton-dependent oligopeptide transporter PepT1.The Journal of physiology · 2011Article
- Functional role of the intracellular loop linking transmembrane domains 6 and 7 of the human dipeptide transporter hPEPT1.The Journal of membrane biology · 2010Article
- Bioavailability through PepT1: the role of computer modelling in intelligent drug design.Current computer-aided drug design · 2010Review
- Mutagenesis and cysteine scanning of transmembrane domain 10 of the human dipeptide transporter.Pharmaceutical research · 2009Article
- APH1 polar transmembrane residues regulate the assembly and activity of presenilin complexes.The Journal of biological chemistry · 2009Article
- Review. The mammalian proton-coupled peptide cotransporter PepT1: sitting on the transporter-channel fence?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2009Review
- Ethanol inhibits functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes.Alcoholism, clinical and experimental research · 2008Article
- Site-directed mutagenesis of Arginine282 suggests how protons and peptides are co-transported by rabbit PepT1.The international journal of biochemistry & cell biology · 2008Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo determine whether R282 in transmembrane segment 7 (TMS7) of hPepT1 forms a salt bridge with D341 in TMS8.
methodsMutated hPepT1 transporters containing point mutations at R282 and/or D341 were transiently transfected into HEK293 cells. Their steady state expression and functional activity were measured using immunoprecipitation and 3H-gly-sar uptake, respectively. Gly-sar uptake by cysteine mutants (R282C and D341C) was also measured in the presence and absence of cysteine-modifying MTS reagents.
resultsThe reverse-charge mutants R282D-hPepT1 and D341R-hPepT1 showed significantly reduced gly-sar uptake, but the double mutant (R282D/D341R-hPepT1) has functionality comparable to that of wild-type hPepT1. Gly-sar uptake by R282C-hPepT1 is reduced, but pre-incubation with 1 mM MTSET, a positively charged cysteine-modifying reagent, restored function to wild-type levels. Similarly, pre-incubation of D341C-hPepT1 with 10 mM MTSES, a negatively charged cysteine-modifying reagent, increased gly-sar uptake compared to unmodified D341C-hPepT1. In contrast, MTSET modification of D341C-hPepT1 (giving a positive charge at position 341) resulted in significant reduction in gly-sar uptake, compared to D341C-hPepT1.
conclusionOur results are consistent with a salt bridge between R282 and D341 in hPepT1, and we use these and other data to propose a role for the R282-D341 charge pair in the hPepT1 translocation mechanism.
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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.