Cryo-EM structure of a type IV secretion system

Kévin Macé (), Abhinav K. Vadakkepat, Adam Redzej, Natalya Lukoyanova, Clasien Oomen, Nathalie Braun, Marta Ukleja, Fang Lu, Tiago R. D. Costa, Elena V. Orlova, David Baker, Qian Cong () and Gabriel Waksman ()
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Kévin Macé: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
Abhinav K. Vadakkepat: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
Adam Redzej: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
Natalya Lukoyanova: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
Clasien Oomen: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
Nathalie Braun: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
Marta Ukleja: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
Fang Lu: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
Tiago R. D. Costa: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
Elena V. Orlova: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College
David Baker: University of Washington, Molecular Engineering and Sciences
Qian Cong: University of Washington, Molecular Engineering and Sciences
Gabriel Waksman: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College

Nature, 2022, vol. 607, issue 7917, 191-196

Abstract: Abstract Bacterial conjugation is the fundamental process of unidirectional transfer of DNAs, often plasmid DNAs, from a donor cell to a recipient cell1. It is the primary means by which antibiotic resistance genes spread among bacterial populations2,3. In Gram-negative bacteria, conjugation is mediated by a large transport apparatus—the conjugative type IV secretion system (T4SS)—produced by the donor cell and embedded in both its outer and inner membranes. The T4SS also elaborates a long extracellular filament—the conjugative pilus—that is essential for DNA transfer4,5. Here we present a high-resolution cryo-electron microscopy (cryo-EM) structure of a 2.8 megadalton T4SS complex composed of 92 polypeptides representing 8 of the 10 essential T4SS components involved in pilus biogenesis. We added the two remaining components to the structural model using co-evolution analysis of protein interfaces, to enable the reconstitution of the entire system including the pilus. This structure describes the exceptionally large protein–protein interaction network required to assemble the many components that constitute a T4SS and provides insights on the unique mechanism by which they elaborate pili.

Date: 2022
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DOI: 10.1038/s41586-022-04859-y

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