Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump.
Anthony W. P. Fitzpatrick,Salomé Llabrés,Arthur Neuberger,James N. Blaza,Xiao Chen Bai,Ui Okada,Satoshi Murakami,Hendrik W. van Veen,Ulrich Zachariae,Sjors H.W. Scheres,Ben F. Luisi,Dijun Du +11 more
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TLDR
In this article, an electron-cryo-microscopy structure of the ABC-type tripartite assembly of Escherichia coli was presented at near-atomic resolution.Abstract:
The MacA-MacB-TolC assembly of Escherichia coli is a transmembrane machine that spans the cell envelope and actively extrudes substrates, including macrolide antibiotics and polypeptide virulence factors. These transport processes are energized by the ATPase MacB, a member of the ATP-binding cassette (ABC) superfamily. We present an electron cryo-microscopy structure of the ABC-type tripartite assembly at near-atomic resolution. A hexamer of the periplasmic protein MacA bridges between a TolC trimer in the outer membrane and a MacB dimer in the inner membrane, generating a quaternary structure with a central channel for substrate translocation. A gating ring found in MacA is proposed to act as a one-way valve in substrate transport. The MacB structure features an atypical transmembrane domain with a closely packed dimer interface and a periplasmic opening that is the likely portal for substrate entry from the periplasm, with subsequent displacement through an allosteric transport mechanism.read more
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Multidrug efflux pumps: structure, function and regulation
Dijun Du,Xuan Wang-Kan,Arthur Neuberger,Hendrik W. van Veen,Klaas M. Pos,Laura J. V. Piddock,Ben F. Luisi +6 more
TL;DR: Recent advances that have increased understanding of the structures and molecular mechanisms of multidrug efflux pumps in bacteria are described, suggesting opportunities for countering their activities.
Journal ArticleDOI
Structural and functional diversity calls for a new classification of ABC transporters.
Christoph Thomas,Stephen G. Aller,Konstantinos Beis,Konstantinos Beis,Elisabeth P. Carpenter,Geoffrey Chang,Lei Chen,Elie Dassa,Michael Dean,Franck Duong Van Hoa,Damian C. Ekiert,Robert Ford,Rachelle Gaudet,Xin Gong,I. Barry Holland,Yihua Huang,Daniel Kahne,Hiroaki Kato,Vassilis Koronakis,Christopher M. Koth,Youngsook Lee,Oded Lewinson,Roland Lill,Enrico Martinoia,Enrico Martinoia,Satoshi Murakami,Heather W. Pinkett,Bert Poolman,Daniel M. Rosenbaum,Balázs Sarkadi,Lutz Schmitt,Erwin Schneider,Yigong Shi,Show Ling Shyng,Dirk Jan Slotboom,Emad Tajkhorshid,D. Peter Tieleman,Kazumitsu Ueda,András Váradi,Po-Chao Wen,Nieng Yan,Peng Zhang,Hongjin Zheng,Jochen Zimmer,Robert Tampé +44 more
TL;DR: A new ABC transporter classification that currently comprises seven different types based on structural homology in the TMDs is proposed, suggesting that during evolution, the ancient motor domains were combined with different transmembrane mechanical systems to orchestrate a variety of cellular processes.
Journal ArticleDOI
Antibiotic resistance mediated by the MacB ABC transporter family : a structural and functional perspective
TL;DR: The MacB ABC transporter forms a tripartite efflux pump with the MacA adaptor protein and TolC outer membrane exit duct to expel antibiotics and export virulence factors from Gram-negative bacteria.
Journal ArticleDOI
Structure and mechanotransmission mechanism of the MacB ABC transporter superfamily
TL;DR: The structure of ATP-bound MacB is presented and precise molecular details of its mechanism are revealed, suggesting that the assembled tripartite pump acts as a molecular bellows to propel substrates through the TolC exit duct, driven by MacB mechanotransmission.
Journal ArticleDOI
Learning the ABCs one at a time: structure and mechanism of ABC transporters.
TL;DR: Recent progress on the structure determination of eukaryotic and bacterial ABC transporters as well as the novel mechanisms that have also been proposed, that fall out of the alternating access mechanism model are reviewed.
References
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