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Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling

Authors :
Mohammad K. Manik
Yun Shi
Sulin Li
Mark A. Zaydman
Neha Damaraju
Samuel Eastman
Thomas G. Smith
Weixi Gu
Veronika Masic
Tamim Mosaiab
James S. Weagley
Steven J. Hancock
Eduardo Vasquez
Lauren Hartley-Tassell
Nestoras Kargios
Natsumi Maruta
Bryan Y. J. Lim
Hayden Burdett
Michael J. Landsberg
Mark A. Schembri
Ivan Prokes
Lijiang Song
Murray Grant
Aaron DiAntonio
Jeffrey D. Nanson
Ming Guo
Jeffrey Milbrandt
Thomas Ve
Bostjan Kobe
Source :
Science (New York, N.Y.). 377(6614)
Publication Year :
2022

Abstract

Cyclic adenosine diphosphate (ADP)–ribose (cADPR) isomers are signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via nicotinamide adenine dinucleotide (oxidized form) (NAD + ) hydrolysis. We show that v-cADPR (2′cADPR) and v2-cADPR (3′cADPR) isomers are cyclized by O-glycosidic bond formation between the ribose moieties in ADPR. Structures of 2′cADPR-producing TIR domains reveal conformational changes that lead to an active assembly that resembles those of Toll-like receptor adaptor TIR domains. Mutagenesis reveals a conserved tryptophan that is essential for cyclization. We show that 3′cADPR is an activator of ThsA effector proteins from the bacterial antiphage defense system termed Thoeris and a suppressor of plant immunity when produced by the effector HopAM1. Collectively, our results reveal the molecular basis of cADPR isomer production and establish 3′cADPR in bacteria as an antiviral and plant immunity–suppressing signaling molecule.

Details

ISSN :
10959203
Volume :
377
Issue :
6614
Database :
OpenAIRE
Journal :
Science (New York, N.Y.)
Accession number :
edsair.doi.dedup.....b97f099648a037f65223ecc550a0069b