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J Biol Chem. 2003 Dec 5;278(49):48898-902. Epub 2003 Sep 23.

Direct involvement of protein myristoylation in myristoylated alanine-rich C kinase substrate (MARCKS)-calmodulin interaction.

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Division of Biomedical Polymer Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.


MARCKS, a major in vivo substrate of protein kinase C, interacts with plasma membranes in a phosphorylation-, myristoylation-, and calmodulin-dependent manner. Although we have previously observed that myristoylated and non-myristoylated MARCKS proteins behave differently during calmodulin-agarose chromatography, the role of protein myristoylation in the MARCKS-calmodulin interaction remained to be elucidated. Here we demonstrate that the myristoyl moiety together with the N-terminal protein domain is directly involved in the MARCKS-calmodulin interaction. Both myristoylated and non-myristoylated recombinant MARCKS bound to calmodulin-agarose at low ionic strengths, but only the former retained the affinity at high ionic strengths. A quantitative analysis obtained with dansyl (5-dimethylaminonaphthalene-1-sulfonyl)-calmodulin showed that myristoylated MARCKS has an affinity higher than the non-myristoylated protein. Furthermore, a synthetic peptide based on the N-terminal sequence was found to bind calmodulin only when it was myristoylated. Only the N-terminal peptide but not the canonical calmodulin-binding domain showed the ionic strength-independent calmodulin binding. A mutation study suggested that the importance of the positive charge in the N-terminal protein domain in the binding.

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