Vibrio parahaemolyticus prey targeting requires autoproteolysis-triggered dimerization of the type VI secretion system effector RhsP

Le Tang; Shuqi Dong; Nadia Rasheed; Hao Weng Wu; Ningkun Zhou; Huadong Li; Meilin Wang; Jun Zheng; Jun He; William Chong Hang Chao

doi:10.1016/j.celrep.2022.111732

Vibrio parahaemolyticus prey targeting requires autoproteolysis-triggered dimerization of the type VI secretion system effector RhsP

Cell Rep. 2022 Dec 6;41(10):111732. doi: 10.1016/j.celrep.2022.111732.

Authors

Le Tang¹, Shuqi Dong², Nadia Rasheed³, Hao Weng Wu³, Ningkun Zhou⁴, Huadong Li³, Meilin Wang³, Jun Zheng⁵, Jun He⁶, William Chong Hang Chao⁷

Affiliations

¹ Faculty of Health Sciences, University of Macau, Macau SAR, China; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, China.
² CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
³ Faculty of Health Sciences, University of Macau, Macau SAR, China.
⁴ Center for Cell Fate and Lineage (CCLA), Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China.
⁵ Faculty of Health Sciences, University of Macau, Macau SAR, China; Institute of Translational Medicine, University of Macau, Macau SAR, China. Electronic address: zhjunyy@gmail.com.
⁶ CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Center for Cell Fate and Lineage (CCLA), Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China. Electronic address: he_jun@gibh.ac.cn.
⁷ Faculty of Health Sciences, University of Macau, Macau SAR, China. Electronic address: williamchao@um.edu.mo.

PMID: 36476863
DOI: 10.1016/j.celrep.2022.111732

Abstract

The rearrangement hotspot (Rhs) repeat is an ancient giant protein fold found in all domains of life. Rhs proteins are polymorphic toxins that could either be deployed as an ABC complex or via a type VI secretion system (T6SS) in interbacterial competitions. To explore the mechanism of T6SS-delivered Rhs toxins, we used the gastroenteritis-associated Vibrio parahaemolyticus as a model organism and identified an Rhs toxin-immunity pair, RhsP-RhsP_I. Our data show that RhsP-dependent prey targeting by V. parahaemolyticus requires T6SS2. RhsP can bind to VgrG2 independently without a chaperone and spontaneously self-cleaves into three fragments. The toxic C-terminal fragment (RhsP_C) can bind to VgrG2 via a VgrG2-interacting region (VIR). Our electron microscopy (EM) analysis reveals that the VIR is encapsulated inside the Rhs β barrel structure and that autoproteolysis triggers a dramatic conformational change of the VIR. This alternative VIR conformation promotes RhsP dimerization, which significantly contributes to T6SS2-mediated prey targeting by V. parahaemolyticus.

Keywords: CP: Microbiology; Rhs proteins; T6SS; WHH nucleases; autoproteolysis; polymorphic toxins.

Publication types

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

MeSH terms

Type VI Secretion Systems*
Vibrio parahaemolyticus*

Substances

Type VI Secretion Systems