The gp27-like Hub of VgrG Serves as Adaptor to Promote Hcp Tube Assembly

Journal of Molecular Biology
Melvin G RenaultEric Cascales

Abstract

Contractile injection systems are multiprotein complexes that use a spring-like mechanism to deliver effectors into target cells. In addition to using a conserved mechanism, these complexes share a common core known as the tail. The tail comprises an inner tube tipped by a spike, wrapped by a contractile sheath, and assembled onto a baseplate. Here, using the type VI secretion system (T6SS) as a model of contractile injection systems, we provide molecular details on the interaction between the inner tube and the spike. Reconstitution into the Escherichia coli heterologous host in the absence of other T6SS components and in vitro experiments demonstrated that the Hcp tube component and the VgrG spike interact directly. VgrG deletion studies coupled to functional assays showed that the N-terminal domain of VgrG is sufficient to interact with Hcp, to initiate proper Hcp tube polymerization, and to promote sheath dynamics and Hcp release. The interaction interface between Hcp and VgrG was then mapped using docking simulations, mutagenesis, and cysteine-mediated cross-links. Based on these results, we propose a model in which the VgrG base serves as adaptor to recruit the first Hcp hexamer and initiates inner tube polymerization.

Citations

Oct 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Xiaoye LiangTao G Dong
Mar 21, 2019·Microbiology·Sarah Coulthurst
Sep 24, 2019·Frontiers in Microbiology·Fernando Navarro-GarciaMariano Larzábal
Nov 14, 2018·Nature Communications·Samuel R DixMark S Thomas
Jun 22, 2019·Annual Review of Microbiology·Jing WangMarek Basler
Jan 12, 2021·Computational and Structural Biotechnology Journal·Cristina E Alvarez-MartinezChuck S Farah
Jun 25, 2020·Cell Reports·Stephanie Sibinelli-SousaEthel Bayer-Santos
Jan 10, 2021·International Journal of Molecular Sciences·Kai-Wei YuLiang Yang
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Julia Monjarás Feria, Miguel A Valvano
Jul 13, 2019·Microbiology Spectrum·Yassine CherrakEric Cascales
Jun 23, 2021·FEMS Microbiology Reviews·Ramses Gallegos-Monterrosa, Sarah J Coulthurst
Jan 6, 2022·PLoS Pathogens·Patrick GüntherStefan Raunser

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