Structure and assembly of type VI secretion system cargo delivery vehicle.

Bacteroides fragilis CP: Microbiology Cryo-EM Hcp-VgrG-PAAR Type VI secretion system cargo delivery vehicle conformational change

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
25 07 2023
Historique:
received: 23 10 2022
revised: 06 05 2023
accepted: 25 06 2023
medline: 31 7 2023
pubmed: 8 7 2023
entrez: 8 7 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 37421630
pii: S2211-1247(23)00792-1
doi: 10.1016/j.celrep.2023.112781
pii:
doi:

Substances chimiques

Type VI Secretion Systems 0
Bacterial Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

112781

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Auteurs

Wenbo He (W)

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 (K)

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.

Zhenlin Ouyang (Z)

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 (Y)

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 (W)

Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Di Wu (D)

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.

Hao An (H)

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.

Yucheng Guo (Y)

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 (M)

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 (Q)

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 (J)

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 (Y)

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 (J)

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 (PM)

Department of Biochemistry, Faculty of Medicine & Dentistry, Edmonton, AB T6G 2R3, Canada.

Fang Zheng (F)

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 (L)

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. Electronic address: zhuli@lzu.edu.cn.

Yurong Wen (Y)

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. Electronic address: yurong.wen@xjtu.edu.cn.

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