7UXS

Crystal structure of the BcThsA SLOG domain in complex with 3'cADPR

7UXS の概要

• エントリーDOI: 10.2210/pdb7uxs/pdb
• 分子名称: BcThsA, (2R,3R,3aS,5S,6R,7S,8R,11R,13S,15aR)-2-(6-amino-9H-purin-9-yl)-3,6,7,11,13-pentahydroxyoctahydro-2H,5H,11H,13H-5,8-epoxy-11lambda~5~,13lambda~5~-furo[2,3-g][1,3,5,9,2,4]tetraoxadiphosphacyclotetradecine-11,13-dione, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: cadpr isomer, bacterial tir, thoeris defense system, thsa, thsb, antiphage defense, nad+, hydrolase
• 由来する生物種: Bacillus subtilis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46063.00

構造登録者

Shi, Y.,Masic, V.,Mosaiab, T.,Ve, T. (登録日: 2022-05-06, 公開日: 2022-09-07, 最終更新日: 2023-10-18)

主引用文献

Manik, M.K.,Shi, Y.,Li, S.,Zaydman, M.A.,Damaraju, N.,Eastman, S.,Smith, T.G.,Gu, W.,Masic, V.,Mosaiab, T.,Weagley, J.S.,Hancock, S.J.,Vasquez, E.,Hartley-Tassell, L.,Kargios, N.,Maruta, N.,Lim, B.Y.J.,Burdett, H.,Landsberg, M.J.,Schembri, M.A.,Prokes, I.,Song, L.,Grant, M.,DiAntonio, A.,Nanson, J.D.,Guo, M.,Milbrandt, J.,Ve, T.,Kobe, B.
Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling.
Science, 377:eadc8969-eadc8969, 2022

PubMed 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.

PubMed: 36048923
DOI: 10.1126/science.adc8969

実験手法

X-RAY DIFFRACTION (1.57 Å)