title: A crystal structure of the cyclic GMP-dependent protein kinase I{beta} dimerization/docking domain reveals molecular details of isoform-specific anchoring.
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.
authors.affiliation: From the Department of Medicine and Cancer Center, San Diego, La Jolla, California 92093.
authors.forename: Darren E
authors.initials: DE
authors.lastname: Casteel
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093.
authors.forename: Eric V
authors.initials: EV
authors.lastname: Smith-Nguyen
authors.affiliation: Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
authors.forename: Banumathi
authors.initials: B
authors.lastname: Sankaran
authors.affiliation: Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Sung H
authors.initials: SH
authors.lastname: Roh
authors.affiliation: From the Department of Medicine and Cancer Center, San Diego, La Jolla, California 92093.
authors.forename: Renate B
authors.initials: RB
authors.lastname: Pilz
authors.affiliation: Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030. Electronic address: ckim@bcm.edu.
authors.forename: Choel
authors.initials: C
authors.lastname: Kim
mesh_terms: 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
chemical_list: D007527:Isoenzymes; D017869:Cyclic GMP-Dependent Protein Kinases
references.citation: Nat Struct Biol. 1996 Dec;3(12):1011-8
references.pmid: 8946854
references.citation: Handb Exp Pharmacol. 2009;(191):137-62
references.pmid: 19089329
references.citation: Handb Exp Pharmacol. 2009;(191):163-93
references.pmid: 19089330
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: Biochemistry. 1990 Oct 23;29(42):9921-8
references.pmid: 2176858
references.citation: Methods Mol Biol. 2008;426:419-35
references.pmid: 18542881
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
references.pmid: 11517324
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: J Biol Chem. 2002 Aug 30;277(35):32003-14
references.pmid: 12082086
references.citation: Nat Med. 2003 Dec;9(12):1506-12
references.pmid: 14608379
references.citation: J Biol Chem. 2003 Dec 12;278(50):50070-9
references.pmid: 12933804
references.citation: Biochemistry. 1991 Oct 1;30(39):9387-95
references.pmid: 1892839
references.citation: Curr Biol. 1993 Oct 1;3(10):658-67
references.pmid: 15335856
references.citation: EMBO J. 2004 Oct 27;23(21):4222-31
references.pmid: 15483626
references.citation: Science. 1991 Oct 25;254(5031):539-44
references.pmid: 1948029
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Jan;57(Pt 1):122-33
references.pmid: 11134934
references.citation: Mol Biol Cell. 2005 Oct;16(10):4765-80
references.pmid: 16055503
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6702-7
references.pmid: 18448676
references.citation: Chembiochem. 2004 Feb 6;5(2):170-6
references.pmid: 14760737
references.citation: J Struct Biol. 2002 Jan-Feb;137(1-2):54-64
references.pmid: 12064933
references.citation: Nature. 2000 Mar 9;404(6774):197-201
references.pmid: 10724174
references.citation: Science. 1999 Nov 19;286(5444):1583-7
references.pmid: 10567269
references.citation: J Biol Chem. 2005 Nov 18;280(46):38211-8
references.pmid: 16166082