期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 279, 期 38, 页码 39374-39382出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M405352200
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资金
- NINDS NIH HHS [NS26086] Funding Source: Medline
The interaction of calmodulin with its target proteins is known to affect the kinetics and affinity of Ca2+ binding to calmodulin. Based on thermodynamic principles, proteins that bind to Ca2+-calmodulin should increase the affinity of calmodulin for Ca2+, while proteins that bind to apo-calmodulin should decrease its affinity for Ca2+. We quantified the effects on Ca2+-calmodulin interaction of two neuronal calmodulin targets: RC3, which binds both Ca2+- and apo-calmodulin, and alphaCaM kinase II, which binds selectively to Ca2+-calmodulin. RC3 was found to decrease the affinity of calmodulin for Ca2+, whereas CaM kinase II increases the calmodulin affinity for Ca2+. Specifically, RC3 increases the rate of Ca2+ dissociation from the C-terminal sites of calmodulin up to 60-fold while having little effect on the rate of Ca2+ association. Conversely, CaM kinase II decreases the rates of dissociation of Ca2+ from both lobes of calmodulin and autophosphorylation of CaM kinase II at Thr(286) induces a further decrease in the rates of Ca2+ dissociation. RC3 dampens the effects of CaM kinase II on Ca2+ dissociation by increasing the rate of dissociation from the C-terminal lobe of calmodulin when in the presence of CaM kinase II. This effect is not seen with phosphorylated CaM kinase II. The results are interpreted according to a kinetic scheme in which there are competing pathways for dissociation of the Ca2+-calmodulin target complex. This work indicates that the Ca2+ binding properties of calmodulin are highly regulated and reveals a role for RC3 in accelerating the dissociation of Ca2+-calmodulin target complexes at the end of a Ca2+ signal.
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