核糖
免疫系统
环ADP核糖
化学
生物化学
生产(经济)
细胞生物学
生物
酶
免疫学
经济
川地34
干细胞
宏观经济学
CD38
作者
M.K. Manik,Yun Shi,Sulin Li,Mark A. Zaydman,Neha Damaraju,Samuel Eastman,Thomas G. Smith,Weixi Gu,Veronika Masic,Tamim Mosaiab,James Weagley,Steven J. Hancock,Eduardo Vasquez,Lauren E. Hartley‐Tassell,Nestoras Kargios,Natsumi Maruta,Bryan Y. J. Lim,Hayden Burdett,Michael J. Landsberg,Mark A. Schembri
出处
期刊:Science
[American Association for the Advancement of Science]
日期:2022-09-01
卷期号:377 (6614)
被引量:99
标识
DOI:10.1126/science.adc8969
摘要
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.
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