Skip to content


  • Poster presentation
  • Open Access

The first crystal structure of cyclic GMP-dependent protein kinase Iβ dimerization/docking domain reveals molecular details of isoform-specific anchoring

  • 1,
  • 2,
  • 3,
  • 4,
  • 4,
  • 1,
  • 2, 5, 6 and
  • 7Email author
BMC Pharmacology20099(Suppl 1):P6

Published: 11 August 2009


  • Salt Bridge
  • Destabilize Effect
  • Multiprotein Complex
  • Molecular Detail
  • Anchor Protein


Cyclic GMP-dependent protein kinase (PKG) is the main mediator of the NO/cGMP signaling pathway and plays a central role in regulating cardiovascular and neuronal functions. Subcellular targeting of PKG provides a mechanism for achieving substrate specificity and is mediated by the most N-terminal ~50 amino acids, which are required for homo-dimerization of the kinase and association with isoform-specific G-k inase a nchoring p roteins (GKAPs). To understand the molecular details of PKG dimerization and targeting to GKAPs, we solved a crystal structure of the PKG Iβ dimerization/docking domain.


The structure reveals two helices wrapping around each other into a left-handed helix and forming a parallel coiled-coil. Two unusual interhelical salt bridges stabilize the coiled-coil, as confirmed by the destabilizing effects of single alanine substitutions. The two interhelical ion pairs flank a patch of acidic residues that are crucial for GKAP binding. This is the first crystal structure available for PKG; it demonstrates not only the molecular details of PKG Iβ dimerization, but also reveal the docking surface for GKAPs.

It is increasingly evident that the fidelity of signal transduction is dependent on the ability of proteins to assemble into pathway specific multiprotein complexes. We also showed that the surrogate domain of the closely related cAMP-dependent protein kinase (PKA) forms an X-type helical bundle (Figure 1), providing a completely different docking surface for binding PKA specific anchoring proteins [1]. The coiled-coil is also a highly important model system for studying fundamental principles in protein folding, stability and specificity.
Figure 1
Figure 1

Structures of the Dimerization/Docking domains.

Authors’ Affiliations

Department of Medicine and Cancer Center, University of California, San Diego, USA
Department of Chemistry and Biochemistry, University of California, San Diego, USA
The Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, USA
Genomics Institute of the Novartis Research Foundation, San Diego, USA
Howard Hughes Medical Institute, University of California, San Diego, USA
Department of Pharmacology, University of California, San Diego, USA
Department of Pharmacology, Baylor College of Medicine, Houston, USA


  1. Kinderman FS, Kim C, von Daake S, Ma Y, Pham BQ, Spraggon G, Xuong NH, Jennings PA, Taylor SS: A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase. Mol Cell. 2006, 24: 397-408. 10.1016/j.molcel.2006.09.015.PubMed CentralView ArticlePubMedGoogle Scholar


© Casteel et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.