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Crystal structure of a myristoylated CAP‐23/NAP‐22 N‐terminal domain complexed with Ca 2+ /calmodulin
Author(s) -
Matsubara Mamoru,
Nakatsu Toru,
Kato Hiroaki,
Taniguchi Hisaaki
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600093
Subject(s) - myristoylation , calmodulin , biology , plasma protein binding , peptide sequence , n terminus , biochemistry , peptide , protein structure , binding domain , binding site , biophysics , microbiology and biotechnology , phosphorylation , enzyme , gene
A variety of viral and signal transduction proteins are known to be myristoylated. Although the role of myristoylation in protein–lipid interaction is well established, the involvement of myristoylation in protein–protein interactions is less well understood. CAP‐23/NAP‐22 is a brain‐specific protein kinase C substrate protein that is involved in axon regeneration. Although the protein lacks any canonical calmodulin (CaM)‐binding domain, it binds CaM with high affinity. The binding of CAP‐23/NAP‐22 to CaM is myristoylation dependent and the N‐terminal myristoyl group is directly involved in the protein–protein interaction. Here we show the crystal structure of Ca 2+ ‐CaM bound to a myristoylated peptide corresponding to the N‐terminal domain of CAP‐23/NAP‐22. The myristoyl moiety of the peptide goes through a hydrophobic tunnel created by the hydrophobic pockets in the N‐ and C‐terminal domains of CaM. In addition to the myristoyl group, several amino‐acid residues in the peptide are important for CaM binding. This is a novel mode of binding and is very different from the mechanism of binding in other CaM–target complexes.