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 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.
Casteel
Darren E
DE
From the Department of Medicine and Cancer Center, San Diego, La Jolla, California 92093.
Smith-Nguyen
Eric V
EV
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093.
Sankaran
Banumathi
B
Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
Roh
Sung H
SH
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
Pilz
Renate B
RB
From the Department of Medicine and Cancer Center, San Diego, La Jolla, California 92093.
Kim
Choel
C
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030. Electronic address: ckim@bcm.edu.
D000818:Animals; D018360:Crystallography, X-Ray; D017869:Cyclic GMP-Dependent Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D016350:Leucine Zippers; D051379:Mice; D008822:Mice, Transgenic; D055503:Protein Multimerization / Q000502:physiology*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D017869:Cyclic GMP-Dependent Protein Kinases
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