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-Structure paper
タイトル | Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling. |
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ジャーナル・号・ページ | Science, Vol. 377, Issue 6614, Page eadc8969, Year 2022 |
掲載日 | 2022年9月30日 |
著者 | 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 / |
PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:36048923 |
手法 | EM (らせん対称) / X線回折 |
解像度 | 1.42 - 3.4 Å |
構造データ | EMDB-26862, PDB-7uxu: PDB-7uwg: PDB-7uxr: PDB-7uxs: PDB-7uxt: |
化合物 | ChemComp-SO4: ChemComp-P6G: ChemComp-HOH: ChemComp-OJC: ChemComp-GOL: ChemComp-PGE: ChemComp-1O4: |
由来 |
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キーワード | HYDROLASE / 2' cADPR / NADase / Bacterial TIR / cADPR isomer / NAD+ / Thoeris defense system / ThsA / ThsB / antiphage defense |