Bacterial cGAS-like enzymes synthesize diverse nucleotide signals

Anonymous — Fri, 01 Mar 2019 07:00:00 +0000

Bacterial cGAS-like enzymes synthesize diverse nucleotide signals Anonymous (not verified) Fri, 03/01/2019 - 00:00

➤Whiteley AT Eaglesham JB de Oliveira Mann CC Morehouse BR Lowey B Nieminen EA Danilchanka O King DS Lee ASY Mekalanos JJ* Kranzusch PJ*

*co-corresponding authors

Nature. 2019 Mar;567(7747):194-199. doi: 10.1038/s41586-019-0953-5. Epub 2019 Feb 20.

Abstract

Cyclic dinucleotides (CDNs) have central roles in bacterial homeostasis and virulence by acting as nucleotide second messengers. Bacterial CDNs also elicit immune responses during infection when they are detected by pattern-recognition receptors in animal cells. Here we perform a systematic biochemical screen for bacterial signalling nucleotides and discover a large family of cGAS/DncV-like nucleotidyltransferases (CD-NTases) that use both purine and pyrimidine nucleotides to synthesize a diverse range of CDNs. A series of crystal structures establish CD-NTases as a structurally conserved family and reveal key contacts in the enzyme active-site lid that direct purine or pyrimidine selection. CD-NTase products are not restricted to CDNs and also include an unexpected class of cyclic trinucleotide compounds. Biochemical and cellular analyses of CD-NTase signalling nucleotides demonstrate that these cyclic di- and trinucleotides activate distinct host receptors and thus may modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts.

News and Commentaries

Pyrimidines and Cyclic Trinucleotides Join the Second Messenger Symphony. [Cell host & microbe 2019]
Diverse bacterial nucleotide signals. [Science Signaling 2019]
Highlighted and discussed in This Week In Microbiology Podcast Episode #206

Links

➤Whiteley AT, Eaglesham JB, de Oliveira Mann CC, Morehouse BR, Lowey B, Nieminen EA, Danilchanka O, King DS, Lee ASY, Mekalanos JJ*, Kranzusch PJ* | Nature. 2019

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Bacterial cGAS-like enzymes synthesize diverse nucleotide signals

Abstract

News and Commentaries

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