The first crystal structure of cyclic GMP-dependent protein kinase Iβ dimerization/docking domain reveals molecular details of isoform-specific anchoring
© Casteel et al; licensee BioMed Central Ltd. 2009
Published: 11 August 2009
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.
This article is published under license to BioMed Central Ltd.