Sandbox 213: Difference between revisions
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'''Calmodulin''' [http://www.rcsb.org/pdb/101/motm_disscussed_entry.do?id=3cln] | '''Calmodulin''' [http://www.rcsb.org/pdb/101/motm_disscussed_entry.do?id=3cln] | ||
[[Image:calmodulin_Ca_site.gif|right|200px]] | |||
Calmodulin contains four Ca<sup>2+</sup> binding sites and the binding of calcium induces a conformational change in calmodulin that can cause the activation of key enzymes such as kinases or phosphatases proteins (especially phosphorylase kinases) which are not necessarily themselves Ca<sup>2+</sup>-sensitive and allows a large diversity of cellular response. | Calmodulin contains four Ca<sup>2+</sup> binding sites and the binding of calcium induces a conformational change in calmodulin that can cause the activation of key enzymes such as kinases or phosphatases proteins (especially phosphorylase kinases) which are not necessarily themselves Ca<sup>2+</sup>-sensitive and allows a large diversity of cellular response. | ||
The calmodulin structure has been determined by NMR. This method reveals that calmodulin is a long molecule which looks like a '''dumbbell''' because it contains '''two globular domains''' (the <scene name='Sandbox_213/N-lobe/1'>N-lobe</scene> and the <scene name='Sandbox_213/C-lobe/1'>C-lobe</scene>) linked by a <scene name='Sandbox_213/flexible α-helix/1'>flexible α-helix</scene> <ref name="Najl V Valeyev1, Declan G Bates1, Pat Heslop-Harrison1,2, Ian Postlethwaite1 and Nikolay V Kotov. Elucidating the mechanisms of cooperative calcium-calmodulin interactions: a structural systems biology approach.BMC Systems Biology 2008, 2:48 doi:[[10.1186/1752-0509-2-48]]"/>. | The calmodulin structure has been determined by NMR. This method reveals that calmodulin is a long molecule which looks like a '''dumbbell''' because it contains '''two globular domains''' (the <scene name='Sandbox_213/N-lobe/1'>N-lobe</scene> and the <scene name='Sandbox_213/C-lobe/1'>C-lobe</scene>) linked by a <scene name='Sandbox_213/flexible α-helix/1'>flexible α-helix</scene> <ref name="Najl V Valeyev1, Declan G Bates1, Pat Heslop-Harrison1,2, Ian Postlethwaite1 and Nikolay V Kotov. Elucidating the mechanisms of cooperative calcium-calmodulin interactions: a structural systems biology approach.BMC Systems Biology 2008, 2:48 doi:[[10.1186/1752-0509-2-48]]"/>. | ||
Each lobe contains a pair of <scene name='Sandbox_213/helix-loop-helix/1'>helix-loop-helix</scene> motifs (called EF-hand or calmodulin-fold) that can bind two Ca<sup>2+</sup> ions. However those lobes do not have the same properties because the C-lobe has higher Ca<sup>2+</sup> affinity than the N-lobe. | Each lobe contains a pair of <scene name='Sandbox_213/helix-loop-helix/1'>helix-loop-helix</scene> motifs (called EF-hand or calmodulin-fold) that can bind two Ca<sup>2+</sup> ions. However those lobes do not have the same properties because the C-lobe has higher Ca<sup>2+</sup> affinity than the N-lobe. | ||
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This encourages the target sequence to adopt an α-helical arrangement so that it occupies the center of a hydrophobic tunnel. | This encourages the target sequence to adopt an α-helical arrangement so that it occupies the center of a hydrophobic tunnel. | ||
The consequence of this interaction is a conformational change in the target, a state that persists only as long as the Ca<sup>2+</sup> concentration remains high <ref name="Fallon JL, Quiocho FA. A closed compact structure of native Ca(2+)-calmodulin. Structure. 2003 Oct;11(10):1303-7. PMID :[[14527397]]"/>. | The consequence of this interaction is a conformational change in the target, a state that persists only as long as the Ca<sup>2+</sup> concentration remains high <ref name="Fallon JL, Quiocho FA. A closed compact structure of native Ca(2+)-calmodulin. Structure. 2003 Oct;11(10):1303-7. PMID :[[14527397]]"/>. | ||
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When the Ca<sup>2+</sup> concentration falls, calcium dissociates and calmodulin is quickly released, inactivating the target. However, at least one important target protein is an exception to this rule. This is CaM-kinase II which can retain its active state after it has been activated by calmodulin. | When the Ca<sup>2+</sup> concentration falls, calcium dissociates and calmodulin is quickly released, inactivating the target. However, at least one important target protein is an exception to this rule. This is CaM-kinase II which can retain its active state after it has been activated by calmodulin. | ||
=CaMII kinase= | =CaMII kinase= | ||