Year: 2022
Type: article
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.
Source: Science
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
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Australian Synchrotron, Griffith University, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, Australian Research Council, National Health and Medical Research Council, National Institute of Neurological Disorders and Stroke
Awards: G2190373191, Nucleoside decoys - metabolic interference in plant defence, Structural biology and therapeutic targeting of axon degeneration, Proteins and glycans in host-pathogen interactions: targets for novel drugs and vaccines, From health to sickness; the metabolomics transition associated with plant disease and defense., Characterization and inhibition of higher-order assembly signalling in Toll-like receptor pathways, Prion-like behaviour in immunity: super-sized signalling platforms?, G578968344, Molecular basis and inhibition of TIR-domain function in Toll-like receptor and neuronal cell-death pathways, G6445618976, A high sensitivity triple quadruple mass spectrometer coupled to an ultra-high pressure liquid chromatograph system for quantitative analysis, Bacterial Plant Diseases Coordination Team, G6989812471, Molecular basis of nucleotide signalling by TIR domain containing proteins, G9000206242
OpenAlex ID: W4294074096