A crystal structure of the cyclic GMP-dependent protein kinase I{beta} dimerization/docking domain reveals molecular details of isoform-specific anchoring

J Biol Chem. 2010 Oct 22;285(43):32684-32688. doi: 10.1074/jbc.C110.161430. Epub 2010 Sep 8.

Abstract

Cyclic GMP-dependent protein kinase (PKG) is a key mediator of the nitric oxide/cGMP signaling pathway and plays a central role in regulating cardiovascular and neuronal functions. The N-terminal ∼50 amino acids of the kinase are required for homodimerization and association with isoform-specific PKG-anchoring proteins (GKAPs), which target the kinase to specific substrates. To understand the molecular details of PKG dimerization and gain insight into its association with GKAPs, we solved a crystal structure of the PKG Iβ dimerization/docking domain. Our structure provides molecular details of this unique leucine/isoleucine zipper, revealing specific hydrophobic and ionic interactions that mediate dimerization and demonstrating the topology of the GKAP interaction surface.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Cyclic GMP-Dependent Protein Kinases / chemistry*
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Leucine Zippers
  • Mice
  • Mice, Transgenic
  • Protein Multimerization / physiology*
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Structure-Activity Relationship

Substances

  • Isoenzymes
  • Cyclic GMP-Dependent Protein Kinases

Associated data

  • PDB/3NMD