3fpp | pdb_00003fpp
Crystal structure of E.coli MacA
Structural highlights
Function[MACA_ECOLI] Part of the tripartite efflux system MacAB-TolC. MacA stimulates the ATPase activity of MacB by promoting the closed ATP-bound state of MacB, increases the capacity of MacB to bind macrolides such as erythromycin, and provides a physical link between MacB and TolC. When overexpressed, the system confers resistance against macrolides composed of 14- and 15-membered lactones but no or weak resistance against 16-membered ones. In addition, MacA binds tightly rough-core lipopolysaccharide (R-LPS), suggesting that the system could also transport R-LPS or a similar glycolipid.[1] [2] [3] [4] [5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIn Gram-negative bacteria, type I protein secretion systems and tripartite drug efflux pumps have a periplasmic membrane fusion protein (MFP) as an essential component. MFPs bridge the outer membrane factor and an inner membrane transporter, although the oligomeric state of MFPs remains unclear. The most characterized MFP AcrA connects the outer membrane factor TolC and the resistance-nodulation-division-type efflux transporter AcrB, which is a major multidrug efflux pump in Escherichia coli. MacA is the periplasmic MFP in the MacAB-TolC pump, where MacB was characterized as a macrolide-specific ATP-binding-cassette-type efflux transporter. Here, we report the crystal structure of E. coli MacA and the experimentally phased map of Actinobacillus actinomycetemcomitans MacA, which reveal a domain orientation of MacA different from that of AcrA. Notably, a hexameric assembly of MacA was found in both crystals, exhibiting a funnel-like structure with a central channel and a conical mouth. The hexameric MacA assembly was further confirmed by electron microscopy and functional studies in vitro and in vivo. The hexameric structure of MacA provides insight into the oligomeric state in the functional complex of the drug efflux pump and type I secretion system. Crystal structure of the periplasmic component of a tripartite macrolide-specific efflux pump.,Yum S, Xu Y, Piao S, Sim SH, Kim HM, Jo WS, Kim KJ, Kweon HS, Jeong MH, Jeon H, Lee K, Ha NC J Mol Biol. 2009 Apr 17;387(5):1286-97. Epub 2009 Feb 28. PMID:19254725[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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