Structure and mechanotransmission mechanism of the MacB ABC transporter superfamily

被引:127
作者
Crow, Allister [1 ]
Greene, Nicholas P. [1 ]
Kaplan, Elise [1 ]
Koronakis, Vassilis [1 ]
机构
[1] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
ABC transporter; X-ray crystallography; tripartite efflux pump; HEAT-STABLE ENTEROTOXIN; MEMBRANE-FUSION PROTEIN; ESCHERICHIA-COLI; ATP-BINDING; MACROLIDE TRANSPORTER; EFFLUX TRANSPORTER; MULTIDRUG EFFLUX; TOLC; HYDROLYSIS; INHIBITORS;
D O I
10.1073/pnas.1712153114
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
MacB is an ABC transporter that collaborates with the MacA adaptor protein and TolC exit duct to drive efflux of antibiotics and enterotoxin STII out of the bacterial cell. Here we present the structure of ATP-bound MacB and reveal precise molecular details of its mechanism. The MacB transmembrane domain lacks a central cavity through which substrates could be passed, but instead conveys conformational changes from one side of the membrane to the other, a process we term mechanotransmission. Comparison of ATP-bound and nucleotide-free states reveals how reversible dimerization of the nucleotide binding domains drives opening and closing of the MacB periplasmic domains via concerted movements of the second transmembrane segment and major coupling helix. We propose that the assembled tripartite pump acts as a molecular bellows to propel substrates through the TolC exit duct, driven by MacB mechanotransmission. Homologs of MacB that do not form tripartite pumps, but share structural features underpinning mechanotransmission, include the LolCDE lipoprotein trafficking complex and FtsEX cell division signaling protein. The MacB architecture serves as the blueprint for understanding the structure and mechanism of an entire ABC transporter superfamily and the many diverse functions it supports.
引用
收藏
页码:12572 / 12577
页数:6
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