Structure and assembly of type VI secretion system cargo delivery vehicle

Wenbo He; Ke Wu; Zhenlin Ouyang; Yixin Bai; Wen Luo; Di Wu; Hao An; Yucheng Guo; Min Jiao; Qian Qin; Jiaxin Zhang; Yi Wu; Junjun She; Peter M. Hwang; Fang Zheng; Li Zhu; Yurong Wen

Cell Reports (Jul 2023)

Structure and assembly of type VI secretion system cargo delivery vehicle

Wenbo He,
Ke Wu,
Zhenlin Ouyang,
Yixin Bai,
Wen Luo,
Di Wu,
Hao An,
Yucheng Guo,
Min Jiao,
Qian Qin,
Jiaxin Zhang,
Yi Wu,
Junjun She,
Peter M. Hwang,
Fang Zheng,
Li Zhu,
Yurong Wen

Affiliations

Wenbo He: Center for Microbiome Research of Med-X Institute, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China
Ke Wu: Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China
Zhenlin Ouyang: Center for Microbiome Research of Med-X Institute, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China
Yixin Bai: Center for Microbiome Research of Med-X Institute, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China
Wen Luo: Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
Di Wu: Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China
Hao An: Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China
Yucheng Guo: The Key Laboratory of Environment and Genes Related to Disease of Ministry of Education Health Science Center, Xi’an Jiaotong University, Xi’an 710061, China
Min Jiao: Center for Microbiome Research of Med-X Institute, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China
Qian Qin: Center for Microbiome Research of Med-X Institute, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China
Jiaxin Zhang: The Key Laboratory of Environment and Genes Related to Disease of Ministry of Education Health Science Center, Xi’an Jiaotong University, Xi’an 710061, China
Yi Wu: The Key Laboratory of Environment and Genes Related to Disease of Ministry of Education Health Science Center, Xi’an Jiaotong University, Xi’an 710061, China
Junjun She: Center for Microbiome Research of Med-X Institute, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China
Peter M. Hwang: Department of Biochemistry, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2R3, Canada
Fang Zheng: The Key Laboratory of Environment and Genes Related to Disease of Ministry of Education Health Science Center, Xi’an Jiaotong University, Xi’an 710061, China
Li Zhu: Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China; Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Electron Microscopy Centre of Lanzhou University, Lanzhou University, Lanzhou 730000, China; Corresponding author
Yurong Wen: Center for Microbiome Research of Med-X Institute, Shaanxi Provincial Key Laboratory of Sepsis in Critical Care Medicine, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, China; The Key Laboratory of Environment and Genes Related to Disease of Ministry of Education Health Science Center, Xi’an Jiaotong University, Xi’an 710061, China; Corresponding author

Journal volume & issue: Vol. 42, no. 7
p. 112781

Abstract

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Summary: Type VI secretion system is widely used in Gram-negative bacteria for injecting toxic effectors into neighboring prokaryotic or eukaryotic cells. Various effectors can be loaded onto the T6SS delivery tube via its core components: Hcp, VgrG, or PAAR. Here, we report 2.8-Å resolution cryo-EM structure of intact T6SS Hcp5-VgrG-PAAR cargo delivery system and crystal structure of unbound Hcp5 from B. fragilis NCTC 9343. Loading of Hcp5 hexameric ring onto VgrG causes expansion of its inner cavity and external surface, explaining how structural changes could be propagated to regulate co-polymerization and surrounding contractile sheath. High-affinity binding between Hcp and VgrG causes entropically unfavorable structuring of long loops. Furthermore, interactions between VgrG trimer and Hcp hexamer are asymmetric, with three of the six Hcp monomers exhibiting a major loop flip. Our study provides insights into the assembly, loading, and firing of T6SS nanomachine that contributes to bacterial inter-species competition and host interactions.

CP: Microbiology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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