3.A.1.122.35
The MacAB drug exporter.  MacB is an ABC transporter that collaborates with the MacA adaptor protein (a membrane fusion protein, MFP) and the TolC exit duct to drive efflux of antibiotics and enterotoxin STII out of the bacterial cell. Crow et al. 2017 presented 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 termed mechanotransmission. Comparison of ATP-bound and nucleotide-free states revealed 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 the major coupling helix. They proposed 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 a blueprint for understanding the structure and mechanism of an entire ABC transporter superfamily and the many diverse functions it supports (Crow et al. 2017). The crystal structure of MacA has been solved (Yum et al. 2009).