Crystal Structure of the Periplasmic Component of a Tripartite Macrolide-Specific Efflux Pump

Authors
Yum, SoohwanXu, YongbinPiao, ShunfuSim, Se-HoonKim, Hong-ManJo, Wol-SoonKim, Kyung-JinKweon, Hee-SeokJeong, Min-HoJeon, HyesungLee, KangseokHa, Nam-Chul
Issue Date
2009-04-17
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Citation
JOURNAL OF MOLECULAR BIOLOGY, v.387, no.5, pp.1286 - 1297
Abstract
In 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. (C) 2009 Elsevier Ltd. All rights reserved.
Keywords
MEMBRANE-FUSION PROTEIN; MULTIDRUG EFFLUX; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; ACRA PROTEINS; TOLC; SYSTEM; TRANSPORTER; CHANNEL; GENES; MEMBRANE-FUSION PROTEIN; MULTIDRUG EFFLUX; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; ACRA PROTEINS; TOLC; SYSTEM; TRANSPORTER; CHANNEL; GENES; multidrug efflux pump; MacA; TolC; AcrA; Gram-negative bacteria
ISSN
0022-2836
URI
https://pubs.kist.re.kr/handle/201004/132564
DOI
10.1016/j.jmb.2009.02.048
Appears in Collections:
KIST Article > 2009
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