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.
Résumé
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.
Domaines
Biochimie, Biologie Moléculaire
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inserm-00497582_edited.pdf (544.86 Ko)
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Ramakrishnan_-A_single_residue_in_a_novel_ADP-ribosyl_cyclase_controls_production_of_the_calcium_mobilizing_messengers_2010.pdf (1.04 Mo)
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Ramakrishnan_-A_single_residue_in_a_novel_ADP-ribosyl_cyclase_controls_production_of_the_calcium_mobilizing_messengers_2010_SD.pdf (19.31 Ko)
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Origine | Fichiers produits par l'(les) auteur(s) |
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Origine | Fichiers produits par l'(les) auteur(s) |
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Format | Autre |
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