title: Crystal structure of a myristoylated CAP-23/NAP-22 N-terminal domain complexed with Ca2+/calmodulin.
abstract: 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 Ca2+-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.
authors.affiliation: Membrane Dynamics Project, Harima Institute at SPring-8, RIKEN, Sayo, Hyogo, Japan. mamoru.matsubara@carnabio.com
authors.forename: Mamoru
authors.initials: M
authors.lastname: Matsubara
authors.forename: Toru
authors.initials: T
authors.lastname: Nakatsu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kato
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Taniguchi
mesh_terms: D002118:Calcium / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry; D002148:Calmodulin-Binding Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D002118:Calcium