Sandbox 213: Difference between revisions
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Calmodulin is able to bind a large range of target molecules. This property is due to its particularly flexible structure that confers the capacity to change its conformation according to the concentration of calcium in the cell. The calmodulin structure has been determined by RMN. This method reveals that calmodulin is a long molecule which looks like a dumbbell because it contains two globular domains (the N-lobe and the C-lobe) linked by a flexible α-helix. Each lobe contains a pair of helix-loop-helix motifs (called EF-hand) that can bind two Ca2+ ions. However those lobes do not have the same properties because the C-lobe has higher Ca2+ affinity than the N-lobe. The two EF-hands are located in the vicinity of each other. Those neighboring sited are very likely to structurally influence each other upon Ca2+ binding to one of them. | Calmodulin is able to bind a large range of target molecules. This property is due to its particularly flexible structure that confers the capacity to change its conformation according to the concentration of calcium in the cell. The calmodulin structure has been determined by RMN. This method reveals that calmodulin is a long molecule which looks like a dumbbell because it contains two globular domains (the N-lobe and the C-lobe) linked by a flexible α-helix. Each lobe contains a pair of helix-loop-helix motifs (called EF-hand) that can bind two Ca2+ ions. However those lobes do not have the same properties because the C-lobe has higher Ca2+ affinity than the N-lobe. The two EF-hands are located in the vicinity of each other. Those neighboring sited are very likely to structurally influence each other upon Ca2+ binding to one of them. | ||
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= | |||
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) | |||
=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. | |||
(IMAGE CALMODULINE FIXEE A QUATRE MOLECULES DE CALCIUM MAIS LA CALMODULINE EST ENCORE DROITE) | |||
=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. | |||
== External Resources == | == External Resources == | ||