4.6 Article

Structure and activity of a bacterial defense-associated 3′-5′ exonuclease

期刊

PROTEIN SCIENCE
卷 31, 期 7, 页码 -

出版社

WILEY
DOI: 10.1002/pro.4374

关键词

bacterial immunity; bacteriophage; CBASS; exonuclease; phage defense

资金

  1. National Institute of Allergy and Infectious Diseases [R21 AI148814]
  2. National Institute of General Medical Sciences [F31 GM137600, R35 GM144121, T32 GM008326, T32 GM127235]

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The CBASS immune systems in bacteria protect against bacteriophage infection by triggering cell death. Cap18, a 3'-5' exonuclease associated with CBASS systems, was found to have nonspecific DNA exonuclease activity and may coordinate with transcription factors to regulate CBASS transcription in response to DNA damage.
The widespread CBASS (cyclic oligonucleotide-based anti-phage signaling system) immune systems in bacteria protect their hosts from bacteriophage infection by triggering programmed cell death. CBASS systems all encode a cyclic oligonucleotide synthase related to eukaryotic cGAS but use diverse regulators and effector proteins including nucleases, phospholipases, and membrane-disrupting proteins to effect cell death. Cap18 is a predicted 3 '-5 ' exonuclease associated with hundreds of CBASS systems, whose structure, biochemical activities, and biological roles remain unknown. Here we show that Cap18 is a DEDDh-family exonuclease related to the bacterial exonucleases RNase T and Orn and has nonspecific 3 '-5 ' DNA exonuclease activity. Cap18 is commonly found in CBASS systems with associated CapW or CapH+CapP transcription factors, suggesting that it may coordinate with these proteins to regulate CBASS transcription in response to DNA damage. These data expand the repertoire of enzymatic activities associated with bacterial CBASS systems and provide new insights into the regulation of these important bacterial immune systems.

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