The Carboxy-Terminal Calcium Binding Sites of Calmodulin Control Calmodulin's Switch from an Activator to an Inhibitor of RYR1
| العنوان: | The Carboxy-Terminal Calcium Binding Sites of Calmodulin Control Calmodulin's Switch from an Activator to an Inhibitor of RYR1 |
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| المؤلفون: | Jack Krol, Susan L. Hamilton, Barbara Y. Williams, George G. Rodney, Kathy Beckingham |
| المصدر: | Biochemistry. 40:12430-12435 |
| بيانات النشر: | American Chemical Society (ACS), 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | Calmodulin, Molecular Sequence Data, chemistry.chemical_element, In Vitro Techniques, Calcium, Models, Biological, Biochemistry, medicine, Animals, Amino Acid Sequence, Binding site, RYR1, Binding Sites, biology, Ryanodine receptor, Activator (genetics), Chemistry, Skeletal muscle, Ryanodine Receptor Calcium Release Channel, musculoskeletal system, Peptide Fragments, Cell biology, Kinetics, medicine.anatomical_structure, Mutagenesis, Site-Directed, biology.protein, Calcium release channel, Rabbits |
| الوصف: | Calcium and calmodulin both regulate the skeletal muscle calcium release channel, also known as the ryanodine receptor, RYR1. Ca(2+)-free calmodulin (apocalmodulin) activates and Ca(2+)-calmodulin inhibits the ryanodine receptor. The conversion of calmodulin from an activator to an inhibitor is due to Ca(2+) binding to calmodulin. We have previously shown that the binding sites for apocalmodulin and Ca(2+)-calmodulin on RYR1 are overlapping with the Ca(2+)-calmodulin site located slightly N-terminal to the apocalmodulin binding site. We now show that mutations of the calcium binding sites in either the N-terminal or the C-terminal lobes of calmodulin decrease the affinity of calmodulin for the ryanodine receptor, suggesting that both lobes interact with RYR1. Mutation of the two C-terminal Ca(2+) binding sites of calmodulin destroys calmodulin's ability to inhibit ryanodine receptor activity at high calcium concentrations. The mutated calmodulin, however, can still bind to RYR1 at both nanomolar and micromolar Ca(2+) concentrations. Mutating the two N-terminal calcium binding sites of calmodulin does not significantly alter calmodulin's ability to inhibit ryanodine receptor activity. These data suggest that calcium binding to the two C-terminal calcium binding sites within calmodulin is responsible for the switching of calmodulin from an activator to an inhibitor of the ryanodine receptor. |
| تدمد: | 1520-4995 0006-2960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::49541ac829615e5af560cd2acccd5b4eTest https://doi.org/10.1021/bi011078aTest |
| رقم الانضمام: | edsair.doi.dedup.....49541ac829615e5af560cd2acccd5b4e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204995 00062960 |
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