Sandbox 213: Difference between revisions
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The affinity of the individual Ca2+ ion binding sites are in the range 10-5-10-6 mol.L-1 and adjacent sites bind Ca2+ with positive cooperativity, so that attachment of the first Ca2+ ion enhances the affinity of its neighbour. This has the effect of making the protein sensitive to small changes in the concentration of Ca2+ within the signaling range. Ca2+-calmodulin itself has no intrinsic catalytic activity. Its action depends on its close association with a target enzyme. | The affinity of the individual Ca2+ ion binding sites are in the range 10-5-10-6 mol.L-1 and adjacent sites bind Ca2+ with positive cooperativity, so that attachment of the first Ca2+ ion enhances the affinity of its neighbour. This has the effect of making the protein sensitive to small changes in the concentration of Ca2+ within the signaling range. Ca2+-calmodulin itself has no intrinsic catalytic activity. Its action depends on its close association with a target enzyme. | ||
'''Three-dimensional structure of apocalmodulin''' | '''==Three-dimensional structure of apocalmodulin==''' | ||
In the absence of bound Ca2+, the helices of calmodulin pack so that their hydrophobic side chains are not exposed. In this form it is unable to interact with its targets5. | In the absence of bound Ca2+, the helices of calmodulin pack so that their hydrophobic side chains are not exposed. In this form it is unable to interact with its targets5. | ||
(IMAGE CALMODULINE SEULE) | (IMAGE CALMODULINE SEULE) | ||
'''Ca2+-bound calmodulin''' | '''==Ca2+-bound calmodulin==''' | ||
Binding of Ca2+ 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. Ca2+-bound calmodulin binds to its targets with high affinity (KD ≈10-9 mol.L-1) 5. | Binding of Ca2+ 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. Ca2+-bound calmodulin binds to its targets with high affinity (KD ≈10-9 mol.L-1) 5. | ||
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'''Calmodulin bound to a target peptide''' | '''==Calmodulin bound to a target peptide==''' | ||
To form the bound state, the central residues of the link region unwind form their α-helical arrangement to form a hinge that allows the molecule to bend and wrap itself around the target. 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. The consequence of this interaction is a conformational change in the target, a state that persists only as long as the Ca2+ concentration remains high5. | To form the bound state, the central residues of the link region unwind form their α-helical arrangement to form a hinge that allows the molecule to bend and wrap itself around the target. 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. The consequence of this interaction is a conformational change in the target, a state that persists only as long as the Ca2+ concentration remains high5. | ||
= External Resources = | |||
*[http://www.rcsb.org/pdb/explore.do?structureId=2d1r Protein Data Bank file on 2CLP] | *[http://www.rcsb.org/pdb/explore.do?structureId=2d1r Protein Data Bank file on 2CLP] | ||
=References= | |||
1. [[↑]]Najl V Valeyev1*, Declan G Bates1, Pat Heslop-Harrison1,2, Ian Postlethwaite1 and Nikolay V Kotov3. 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]][http://www.biomedcentral.com/1752-0509/2/48] | 1. [[↑]]Najl V Valeyev1*, Declan G Bates1, Pat Heslop-Harrison1,2, Ian Postlethwaite1 and Nikolay V Kotov3. 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]][http://www.biomedcentral.com/1752-0509/2/48] | ||
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5. [[↑]]Colbran RJ, Brown AM. Calcium/calmodulin-dependent protein kinase II and synaptic plasticity.Curr Opin Neurobiol. 2004 Jun;14(3):[[318-27]]. Vanderbilt University Medical Center, Nashville, Tennessee 37232-0615, USA. roger.colbran@vanderbilt.edu [http://www.ncbi.nlm.nih.gov/pubmed/15194112] | 5. [[↑]]Colbran RJ, Brown AM. Calcium/calmodulin-dependent protein kinase II and synaptic plasticity.Curr Opin Neurobiol. 2004 Jun;14(3):[[318-27]]. Vanderbilt University Medical Center, Nashville, Tennessee 37232-0615, USA. roger.colbran@vanderbilt.edu [http://www.ncbi.nlm.nih.gov/pubmed/15194112] | ||
=Proteopedia Page Contributors and Editor= | |||
Saphia TONAZZINI, Charlène PLANCHENAULT | Saphia TONAZZINI, Charlène PLANCHENAULT | ||
