6V98

Crystal structure of Type VI secretion system effector, TseH (VCA0285)

Summary for 6V98

• Entry DOI: 10.2210/pdb6v98/pdb
• Descriptor: Cysteine hydrolase, CALCIUM ION (3 entities in total)
• Functional Keywords: effector, type 6 secretion system, cysteine hydrolase, structural genomics, center for structural genomics of infectious diseases, csgid, hydrolase
• Biological source: Vibrio cholerae
• Total number of polymer chains: 1
• Total formula weight: 22748.75

Authors

Watanabe, N.,Hersch, S.J.,Dong, T.G.,Savchenko, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2019-12-13, release date: 2020-01-15, Last modification date: 2024-11-20)

Primary citation

Hersch, S.J.,Watanabe, N.,Stietz, M.S.,Manera, K.,Kamal, F.,Burkinshaw, B.,Lam, L.,Pun, A.,Li, M.,Savchenko, A.,Dong, T.G.
Envelope stress responses defend against type six secretion system attacks independently of immunity proteins.
Nat Microbiol, 5:706-714, 2020

PubMed Abstract: The arms race among microorganisms is a key driver in the evolution of not only the weapons but also defence mechanisms. Many Gram-negative bacteria use the type six secretion system (T6SS) to deliver toxic effectors directly into neighbouring cells. Defence against effectors requires cognate immunity proteins. However, here we show immunity-independent protection mediated by envelope stress responses in Escherichia coli and Vibrio cholerae against a V. cholerae T6SS effector, TseH. We demonstrate that TseH is a PAAR-dependent species-specific effector highly potent against Aeromonas species but not against its V. cholerae immunity mutant or E. coli. A structural analysis reveals TseH is probably a NlpC/P60-family cysteine endopeptidase. We determine that two envelope stress-response pathways, Rcs and BaeSR, protect E. coli from TseH toxicity by mechanisms including capsule synthesis. The two-component system WigKR (VxrAB) is critical for protecting V. cholerae from its own T6SS despite expressing immunity genes. WigR also regulates T6SS expression, suggesting a dual role in attack and defence. This deepens our understanding of how bacteria survive T6SS attacks and suggests that defence against the T6SS represents a major selective pressure driving the evolution of species-specific effectors and protective mechanisms mediated by envelope stress responses and capsule synthesis.

PubMed: 32094588
DOI: 10.1038/s41564-020-0672-6

Experimental method

X-RAY DIFFRACTION (1.8 Å)