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研究揭示环ADP核糖异构体的生产、化学结构和免疫信号传递
作者:小柯机器人 发布时间:2022/9/4 19:44:57

澳大利亚昆士兰大学Bostjan Kobe、格里菲斯大学Thomas Ve等研究人员合作揭示环ADP核糖异构体的生产、化学结构和免疫信号传递。相关论文于2022年9月1日在线发表在《科学》杂志上。

研究人员表示,环ADP核糖(cADPR)异构体是由细菌和植物Toll/白细胞介素-1受体(TIR)结构域通过NAD+水解产生的信号分子。

研究人员表明,v-cADPR(2′cADPR)和v2-cADPR(3′cADPR)异构体通过ADPR中核糖分子之间的O-糖苷键形成而环化。产生2′cADPR的TIR结构显示了导致活性组装的构象变化,这与Toll样受体适应体TIR结构域的构象变化相似。基因突变揭示了一个保守的色氨酸对环化至关重要。

结果表明,3′cADPR是来自细菌抗噬菌体防御系统的ThsA效应蛋白的激活剂,当由效应蛋白HopAM1产生时是植物免疫的抑制剂。总之,这些结果揭示了cADPR异构体产生的分子基础,并确立了细菌中的3′cADPR是一种抗病毒和抑制植物免疫的信号分子。

附:英文原文

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

Author: 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

Issue&Volume: 2022-09-01

Abstract: Cyclic ADP ribose (cADPR) isomers are signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via 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 leading to an active assembly that resembles those of Toll-like receptor adaptor TIR domains. Mutagenesis reveals a conserved tryptophan essential for cyclization. We show that 3′cADPR is an activator of ThsA effector proteins from bacterial anti-phage defense systems 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.

DOI: adc8969

Source: https://www.science.org/doi/10.1126/science.adc8969

 

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037