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Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria

Alav, Ilyas and Kobylka, Jessica and Kuth, Miriam S and Pos, Klaas M and Picard, Martin and Blair, Jessica MA and Bavro, Vassiliy N (2021) 'Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria.' Chemical Reviews, 121 (9). pp. 5479-5596. ISSN 0009-2665

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Tripartite efflux pumps and the related type 1 secretion systems (T1SSs) in Gram-negative organisms are diverse in function, energization, and structural organization. They form continuous conduits spanning both the inner and the outer membrane and are composed of three principal components—the energized inner membrane transporters (belonging to ABC, RND, and MFS families), the outer membrane factor channel-like proteins, and linking the two, the periplasmic adaptor proteins (PAPs), also known as the membrane fusion proteins (MFPs). In this review we summarize the recent advances in understanding of structural biology, function, and regulation of these systems, highlighting the previously undescribed role of PAPs in providing a common architectural scaffold across diverse families of transporters. Despite being built from a limited number of basic structural domains, these complexes present a staggering variety of architectures. While key insights have been derived from the RND transporter systems, a closer inspection of the operation and structural organization of different tripartite systems reveals unexpected analogies between them, including those formed around MFS- and ATP-driven transporters, suggesting that they operate around basic common principles. Based on that we are proposing a new integrated model of PAP-mediated communication within the conformational cycling of tripartite systems, which could be expanded to other types of assemblies.

Item Type: Article
Uncontrolled Keywords: Gram-Negative Bacteria; Bacterial Outer Membrane Proteins; Membrane Transport Proteins; ATP-Binding Cassette Transporters; Protein Conformation; Structure-Activity Relationship; Molecular Dynamics Simulation; Type I Secretion Systems
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 06 May 2021 14:22
Last Modified: 18 Aug 2022 12:31

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