A single residue in a novel ADP-ribosyl cyclase controls production of the calcium-mobilizing messengers cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate.

Abstract : Cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate are ubiquitous calcium-mobilizing messengers produced by the same family of multifunctional enzymes, the ADP-ribosyl cyclases. Not all ADP-ribosyl cyclases have been identified, and how production of different messengers is achieved is incompletely understood. Here, we report the cloning and characterization of a novel ADP-ribosyl cyclase (SpARC4) from the sea urchin, a key model organism for the study of calcium-signaling pathways. Like several other members of the ADP-ribosyl cyclase superfamily, SpARC4 is a glycoprotein targeted to the plasma membrane via a glycosylphosphatidylinositol anchor. However, unlike most other members, SpARC4 shows a remarkable preference for producing cyclic ADP-ribose over nicotinic acid adenine dinucleotide phosphate. Mutation of a single residue (tyrosine 142) within a noncanonical active site reversed this striking preference. Our data highlight further diversification of this unusual enzyme family, provide mechanistic insight into multifunctionality, and suggest that different ADP-ribosyl cyclases are fine-tuned to produce specific calcium-mobilizing messengers.
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Article dans une revue
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (26), pp.19900-9. 〈10.1074/jbc.M110.105312〉
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Soumis le : mardi 12 avril 2011 - 11:06:19
Dernière modification le : vendredi 22 décembre 2017 - 01:08:30

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Latha Ramakrishnan, Hélène Muller-Steffner, Christophe Bosc, Victor Vacquier, Francis Schuber, et al.. A single residue in a novel ADP-ribosyl cyclase controls production of the calcium-mobilizing messengers cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2010, 285 (26), pp.19900-9. 〈10.1074/jbc.M110.105312〉. 〈inserm-00497582〉

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