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

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 PK...

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Bibliographic Details
Published in:The Journal of biological chemistry 2010-10, Vol.285 (43), p.32684-32688
Main Authors: Casteel, Darren E, Smith-Nguyen, Eric V, Sankaran, Banumathi, Roh, Sung H, Pilz, Renate B, Kim, Choel
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:1083-351X
DOI:10.1074/jbc.C110.161430