Sandbox 213: Difference between revisions

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Calmodulin uses a linear sequence of 12 amino acids to bind Ca<sup>2+</sup>.
Calmodulin uses a linear sequence of 12 amino acids to bind Ca<sup>2+</sup>.
Binding of Ca<sup>2+</sup> to the four sites induces a large conformational change causing the terminal helices to expose hydrophobic surfaces and also a long central α-helical segment. Ca<sup>2+</sup>-bound calmodulin binds to its targets with high affinity (K<sub>D</sub>≈10<sup>&minus;9</sup> mol.L<sup>&minus;1</sup>)<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]]"/>.
Binding of Ca<sup>2+</sup> to the four sites induces a large conformational change causing the terminal helices to expose hydrophobic surfaces and also a long central α-helical segment. Ca<sup>2+</sup>-bound calmodulin binds to its targets with high affinity (K<sub>D</sub>≈10<sup>&minus;9</sup> mol.L<sup>&minus;1</sup>)<ref name="Colbran RJ, Brown AM. Calcium/calmodulin-dependent protein kinase II and synaptic plasticity. Curr Opin Neurobiol. 2004 Jun;14(3):318-27. PMID:15194112 doi:[[10.1016/j.conb.2004.05.008
 
]]"/>.
 


    
    
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The N-terminal and C-terminal regions approach each other and by their hydrophobic surfaces bind to it, rather like two hands holding a rope.  
The N-terminal and C-terminal regions approach each other and by their hydrophobic surfaces bind to it, rather like two hands holding a rope.  
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="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 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="Colbran RJ, Brown AM. Calcium/calmodulin-dependent protein kinase II and synaptic plasticity. Curr Opin Neurobiol. 2004 Jun;14(3):318-27. PMID:15194112 doi:[[10.1016/j.conb.2004.05.008]]"/>.




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