title: The typically disordered N-terminus of PKA can fold as a helix and project the myristoylation site into solution.
abstract: Protein kinases comprise the major enzyme family critically involved in signal transduction pathways; posttranslational modifications affect their regulation and determine signaling states. The prototype protein kinase A (PKA) possesses an N-terminal alpha-helix (Helix A) that is atypical for kinases and is thus a major distinguishing feature of PKA. Its physiological function may involve myristoylation at the N-terminus and modulation via phosphorylation at serine 10. Here we describe an unusual structure of an unmyristoylated PKA, unphosphorylated at serine 10, with a completely ordered N-terminus. Using standard conditions (e.g., PKI 5-24, ATP site ligand, MEGA-8), a novel 2-fold phosphorylated PKA variant showed the ordered N-terminus in a new crystal packing arrangement. Thus, the critical factor for structuring the N-terminus is apparently the absence of phosphorylation of Ser10. The flexibility of the N-terminus, its myristoylation, and the conformational dependence on the phosphorylation state are consistent with a functional role for myristoylation.
authors.affiliation: Abteilung Strukturforschung, Max-Planck-Institut fuer Biochemie, 82152 Martinsried, Germany. breitenl@biochem.mpg.de
authors.forename: Christine
authors.initials: C
authors.lastname: Breitenlechner
authors.forename: Richard A
authors.initials: RA
authors.lastname: Engh
authors.forename: Robert
authors.initials: R
authors.lastname: Huber
authors.forename: Volker
authors.initials: V
authors.lastname: Kinzel
authors.forename: Dirk
authors.initials: D
authors.lastname: Bossemeyer
authors.forename: Michael
authors.initials: M
authors.lastname: Gassel
mesh_terms: D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019814:Myristic Acid / Q000378:metabolism*; D010766:Phosphorylation; D017510:Protein Folding; D012694:Serine / Q000378:metabolism
chemical_list: D019814:Myristic Acid; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases