{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Singh H"],"funding":["Medical Research Council","Biotechnology and Biological Sciences Research Council"],"pagination":["12387"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4979069"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7"],"pubmed_abstract":["ATP-binding cassette transporters mediate the transbilayer movement of a vast number of substrates in or out of cells in organisms ranging from bacteria to humans. Current alternating access models for ABC exporters including the multidrug and Lipid A transporter MsbA from Escherichia coli suggest a role for nucleotide as the fundamental source of free energy. These models involve cycling between conformations with inward- and outward-facing substrate-binding sites in response to engagement and hydrolysis of ATP at the nucleotide-binding domains. Here we report that MsbA also utilizes another major energy currency in the cell by coupling substrate transport to a transmembrane electrochemical proton gradient. The dependence of ATP-dependent transport on proton coupling, and the stimulation of MsbA-ATPase by the chemical proton gradient highlight the functional integration of both forms of metabolic energy. These findings introduce ion coupling as a new parameter in the mechanism of this homodimeric ABC transporter."],"journal":["Nature communications"],"pubmed_title":["ATP-dependent substrate transport by the ABC transporter MsbA is proton-coupled."],"pmcid":["PMC4979069"],"funding_grant_id":["G0401165","BB/I002383/1","BB/K017713/1","BB/C004663/1","MC_PC_14116"],"pubmed_authors":["Singh H","van Veen HW","Howard J","Wei SL","Deery MJ","Velamakanni S"],"additional_accession":[]},"is_claimable":false,"name":"ATP-dependent substrate transport by the ABC transporter MsbA is proton-coupled.","description":"ATP-binding cassette transporters mediate the transbilayer movement of a vast number of substrates in or out of cells in organisms ranging from bacteria to humans. Current alternating access models for ABC exporters including the multidrug and Lipid A transporter MsbA from Escherichia coli suggest a role for nucleotide as the fundamental source of free energy. These models involve cycling between conformations with inward- and outward-facing substrate-binding sites in response to engagement and hydrolysis of ATP at the nucleotide-binding domains. Here we report that MsbA also utilizes another major energy currency in the cell by coupling substrate transport to a transmembrane electrochemical proton gradient. The dependence of ATP-dependent transport on proton coupling, and the stimulation of MsbA-ATPase by the chemical proton gradient highlight the functional integration of both forms of metabolic energy. These findings introduce ion coupling as a new parameter in the mechanism of this homodimeric ABC transporter.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Aug","modification":"2025-04-21T18:59:37.564Z","creation":"2019-03-27T02:20:16Z"},"accession":"S-EPMC4979069","cross_references":{"pubmed":["27499013"],"doi":["10.1038/ncomms12387"]}}