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

Mohammad K Manik^#^{1

2}, Yun Shi^#³, Sulin Li^#^{1

2}, Mark A Zaydman⁴, Neha Damaraju^{5

6}, Samuel Eastman⁷, Thomas G Smith⁸, Weixi Gu^{1

2}, Veronika Masic³, Tamim Mosaiab³, James S Weagley⁹, Steven J Hancock^{1

2}, Eduardo Vasquez³, Lauren Hartley-Tassell³, Nestoras Kargios¹⁰, Natsumi Maruta^{1

2}, Bryan Y J Lim^{1

2}, Hayden Burdett^{1

2}, Michael J Landsberg^{1

2}, Mark A Schembri^{1

2}, Ivan Prokes¹¹, Lijiang Song¹¹, Murray Grant¹⁰, Aaron DiAntonio^{4

5}, Jeffrey D Nanson^{1

2}, Ming Guo¹², Jeffrey Milbrandt⁴, Thomas Ve³, Bostjan Kobe^{1

2

13}

Affiliations

¹ School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
² Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD 4072, Australia.
³ Institute for Glycomics, Griffith University, Southport, QLD 4222, Australia.
⁴ Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63100, USA.
⁵ Department of Developmental Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63100, USA.
⁶ Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO 63100, USA.
⁷ Department of Plant Pathology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
⁸ Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
⁹ Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
¹⁰ School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
¹¹ Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
¹² Department of Agronomy and Horticulture, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
¹³ The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.

^# Contributed equally.

PMID: 36048923
DOI: 10.1126/science.adc8969

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

Mohammad K Manik et al. Science. 2022.

. 2022 Sep 30;377(6614):eadc8969.

doi: 10.1126/science.adc8969. Epub 2022 Sep 30.

Authors

Affiliations

¹ School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
² Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD 4072, Australia.
³ Institute for Glycomics, Griffith University, Southport, QLD 4222, Australia.
⁴ Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63100, USA.
⁵ Department of Developmental Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63100, USA.
⁶ Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO 63100, USA.
⁷ Department of Plant Pathology, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
⁸ Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
⁹ Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
¹⁰ School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
¹¹ Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
¹² Department of Agronomy and Horticulture, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
¹³ The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD 4072, Australia.

^# Contributed equally.

PMID: 36048923
DOI: 10.1126/science.adc8969

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

Affiliations

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

Authors

Affiliations

Abstract

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources