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

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

doi:10.1126/science.adc8969

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

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. SchembriIvan Prokes, Lijiang Song, Murray Grant, Aaron DiAntonio, Jeffrey D. Nanson, Ming Guo, Jeffrey Milbrandt, Thomas Ve, Bostjan Kobe

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

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.

Original language	English (US)
Article number	eadc8969
Journal	Science
Volume	377
Issue number	6614
DOIs	https://doi.org/10.1126/science.adc8969
State	Published - Sep 30 2022
Externally published	Yes

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© 2022 American Association for the Advancement of Science. All rights reserved.

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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., ... Kobe, B. (2022). Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling. Science, 377(6614), Article eadc8969. https://doi.org/10.1126/science.adc8969

Manik, MK, Shi, Y, Li, S, Zaydman, MA, Damaraju, N, Eastman, S, Smith, TG, Gu, W, Masic, V, Mosaiab, T, Weagley, JS, Hancock, SJ, Vasquez, E, Hartley-Tassell, L, Kargios, N, Maruta, N, Lim, BYJ, Burdett, H, Landsberg, MJ, Schembri, MA, Prokes, I, Song, L, Grant, M, DiAntonio, A, Nanson, JD, Guo, M, Milbrandt, J, Ve, T & Kobe, B 2022, 'Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling', Science, vol. 377, no. 6614, eadc8969. https://doi.org/10.1126/science.adc8969

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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.",

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AU - Damaraju, Neha

AU - Eastman, Samuel

AU - Smith, Thomas G.

AU - Gu, Weixi

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AU - Mosaiab, Tamim

AU - Weagley, James S.

AU - Hancock, Steven J.

AU - Vasquez, Eduardo

AU - Hartley-Tassell, Lauren

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AU - Maruta, Natsumi

AU - Lim, Bryan Y.J.

AU - Burdett, Hayden

AU - Landsberg, Michael J.

AU - Schembri, Mark A.

AU - Prokes, Ivan

AU - Song, Lijiang

AU - Grant, Murray

AU - DiAntonio, Aaron

AU - Nanson, Jeffrey D.

AU - Guo, Ming

AU - Milbrandt, Jeffrey

AU - Ve, Thomas

AU - Kobe, Bostjan

PY - 2022/9/30

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N2 - 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.

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

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