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FUNCTION Outer membrane channel, which is required for the function of several efflux systems such as AcrAB-TolC, AcrEF-TolC, EmrAB-TolC and MacAB-TolC (PubMed:11274125, PubMed:15228545, PubMed:18955484, PubMed:28355133, PubMed:28504659, PubMed:31201302, PubMed:40083904, PubMed:40461577, PubMed:6337123). These systems are involved in export of antibiotics and other toxic compounds from the cell (PubMed:11274125, PubMed:18955484, PubMed:28504659). As part of the system, involved in the efflux of the immediate heme precursor, protoporphyrin IX (PPIX), which is probably an endogenous substrate (PubMed:25257218). Plays a role in substrate specificity during efflux (PubMed:32850959). TolC is also involved in import of colicin E1 into the cells (PubMed:23176499, PubMed:35199644).ACTIVITY REGULATION In vitro, inhibited by hexaamminecobalt(3+).SUBUNIT Homotrimer (PubMed:15342230, PubMed:16079137, PubMed:9044294). Part of tripartite efflux systems, which are composed of an inner membrane transporter, a periplasmic membrane fusion protein, and an outer membrane component, TolC (PubMed:15228545, PubMed:16079137, PubMed:18955484, PubMed:19342493, PubMed:28355133, PubMed:31201302, PubMed:40083904). The complexes form a large protein conduit and can translocate molecules across both the inner and outer membranes (PubMed:15228545, PubMed:18955484, PubMed:40083904). TolC interacts with the membrane fusion proteins AcrA, EmrA and MacA (PubMed:15228545, PubMed:18955484, PubMed:19805313, PubMed:21325274). 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:15228545, PubMed:16079137, 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:28355133). 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). 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 complex shifts to the closed state (PubMed:31201302). 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:28355133). Component of the MacAB-TolC efflux pump complex, composed of an inner membrane ABC-type transporter, MacB, a periplasmic membrane fusion protein, MacA, and an outer membrane component, TolC (PubMed:28504659, PubMed:40083904, PubMed:40461577). In the absence of substrate, MacA and TolC may form a bipartite complex (PubMed:40083904, PubMed:40461577). Interacts with colicin E1 (via N-terminal region); interaction can inhibit efflux and potentiate the effects of antibiotics on E.coli strain BW25113 (PubMed:35199644).INTERACTION Probably forms a continuous, solvent-accessible conduit: a 'channel-tunnel' over 140 Angstroms long that spans both the outer membrane and periplasmic space (PubMed:10879525). The periplasmic or proximal end of the tunnel may be sealed by sets of coiled helices (PubMed:10879525).DISRUPTION PHENOTYPE Cannot grow on efflux substrates novobiocin or fusidic acid (PubMed:15228545). Cell envelope weakening and increases outer membrane permeability (PubMed:38628966). Acquires sensitivity to chemical inhibitors of ATP-dependent lipid A-core flippase MsbA (PubMed:38628966). Impairs growth in combination with CRISPRi-mediated knockdown of msbA (PubMed:38628966). Accumulates 9 times more protoporphyrin IX (PPIX) than the corresponding complemented strain; in the presence of overexpression of the Dyp peroxidase, yfeX (PubMed:25257218). Total intracellular porphyrins increase about 25-fold in the presence of iron chelators, in a combined tolC and entF mutant background (PubMed:25257218).SIMILARITY Belongs to the outer membrane factor (OMF) (TC 1.B.17) family.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.
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