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FUNCTION The inner membrane transporter component of the AcrAB-TolC efflux system which confers multidrug resistance (PubMed:16915237, PubMed:16946072, PubMed:17194213, PubMed:23010927, PubMed:28355133, PubMed:31201302). The AcrAB-TolC efflux system has a broad substrate specificity, acting as a substrate:proton antiporter, using proton motive force to export substrates (PubMed:16915237, PubMed:16946072, PubMed:17015667, PubMed:17194213, PubMed:19023693, PubMed:19425588, PubMed:22121023, PubMed:23010927, PubMed:25248080). Oxidized fatty acids may be one class of native substrate for AcrB, as part of the AcrAB-TolC efflux protein complex (PubMed:33785633). AcrB is also a component of the AcrABZ-TolC efflux system, where the small accessory protein AcrZ, together with membrane lipids, may influence the specificity of drug export (PubMed:23010927, PubMed:24747401, PubMed:32348749).FUNCTION (Microbial infection) Involved in contact-dependent growth inhibition (CDI), acts downstream of BamA, the receptor for CDI (PubMed:18761695). Its role in CDI is independent of the AcrAB-TolC efflux pump complex (PubMed:18761695).ACTIVITY REGULATION Antibiotic efflux is inhibited by pyridopyrimidine derivatives, such as ABI-PP, acting by binding to a hydrophobic pocket and thereby preventing the conformational changes in AcrB involved in substrate efflux.SUBUNIT Homotrimer, with large porter and funnel domains (PubMed:10920254, PubMed:12374972, PubMed:12738864, PubMed:15228545, PubMed:16079137, PubMed:16915237, PubMed:16946072, PubMed:17194213, PubMed:19023693, PubMed:28355133, PubMed:31201302). Extends into the periplasm, where the trimer interacts with AcrA and TolC (PubMed:10920254, PubMed:12374972, PubMed:12738864, PubMed:15228545, PubMed:16079137, PubMed:16915237, PubMed:16946072, PubMed:17194213, PubMed:19023693, PubMed:28355133, PubMed:31201302). Component of the AcrAB-TolC multidrug efflux complex, composed of six AcrA subunits forming a hexameric tube, binding to an AcrB trimer, which interact with the trimeric TolC outer membrane channel protein (PubMed:10920254, PubMed:12374972, PubMed:12738864, PubMed:15228545, PubMed:16079137, PubMed:16915237, PubMed:16946072, PubMed:17194213, PubMed:24747401, PubMed:28355133, PubMed:31201302). TolC is thought to not contact AcrB stably; instead, AcrA joins AcrB and TolC by forming a funnel-like hexamer anchored to the inner membrane (PubMed:15228545, PubMed:24747401, PubMed:28355133, PubMed:31201302). AcrA may initially form a hexameric ring complex with AcrB, in a bipartite complex, which may be stabilized by binding of AcrA with the peptidoglycan layer, prior to forming the full AcrAB-TolC efflux pump complex (PubMed:22308040, PubMed:28355133, PubMed:31201302). Contact between AcrA-AcrB and TolC may prompt a conformational change in the presence of substrate, allowing the periplasmic gate to open (PubMed:28355133, PubMed:31201302). Each AcrB protomer adopts one of three different conformational states, probably cycling between access, binding, and extrusion of substrate (PubMed:10920254, PubMed:12374972, PubMed:12738864, PubMed:15228545, PubMed:16079137, PubMed:16915237, PubMed:16946072, PubMed:17015667, PubMed:17194213, PubMed:19023693, PubMed:19425588, PubMed:25248080, PubMed:28355133, PubMed:31201302). Several charged residues in the transmembrane region of AcrB may constitute a proton translocation pathway, playing a key energetic role in the conformational changes driving efflux (PubMed:17015667, PubMed:19425588, PubMed:25248080). It is thought that, under high intracellular substrate concentration, AcrB ejects substrate into the tunnel formed by AcrA-TolC; as the substrate level declines, conformational changes in AcrB cause efflux to reduce and stop and the whole complex shifts to the closed state (PubMed:16915237, PubMed:16946072, PubMed:17194213, PubMed:25248080, PubMed:28355133, PubMed:31201302). Interacts with AcrZ; the interaction is direct (PubMed:23010927, PubMed:32348749). Component of the AcrABZ-TolC efflux pump complex, composed of six AcrA subunits forming a hexameric tube binding to an AcrB trimer, which interact with the trimeric TolC outer membrane channel protein; AcrZ interacts directly with AcrB, probably in 1:1 stoichiometry (PubMed:23010927, PubMed:24747401, PubMed:28355133, PubMed:32348749).INTERACTION Positively regulated by MarA, Rob and SoxS transcriptional regulators (at protein level).DISRUPTION PHENOTYPE Loss of susceptibility to contact-dependent growth inhibition (CDI); inhibiting cells still contact the target (PubMed:18761695). Hypersensitive to the bile acid, deoxycholate; growth is severely impaired (PubMed:19023693). Increases susceptibility to antibiotic substrates of the AcrAB-TolC efflux pump, including oxacillin, novobiocin and erythromycin (PubMed:33785633). Increases intracellular accumulation of the dye Hoescht 33342, but not ethidium bromide (PubMed:33785633).MISCELLANEOUS Pyridopyrimidine derivatives, such as ABI-PP, are not exported by the AcrAB-TolC efflux pump, bind tightly to a AcrB hydrophobic pocket and so potentiate the activities of antibiotics such as erythromycin.SIMILARITY Belongs to the resistance-nodulation-cell division (RND) (TC 2.A.6) family.
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