Casteel, Darren E

Hampton, Eric N

Kim, Choel

Pilz, Renate B

Sankaran, Banumathi

Smith-Nguyen, Eric V

Spraggon, Glen

Taylor, Susan S

BMC Pharmacology

English

PubMed

Springer - Publisher Connector

BioMed CentralBMC Pharmacology
ssOpen AccePoster presentation
The first crystal structure of cyclic GMP-dependent protein kinase 
I dimerization/docking domain reveals molecular details of 
isoform-specific anchoring
Darren E Casteel1, Eric V Smith-Nguyen2, Banumathi Sankaran3, 
Glen Spraggon4, Eric N Hampton4, Renate B Pilz1, Susan S Taylor2,5,6 and 
Choel Kim*7
Address: 1Department of Medicine and Cancer Center, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0654, USA, 
2Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0654, USA, 3The Berkeley 
Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA, 4Genomics Institute of the Novartis Research 
Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA, 5Howard Hughes Medical Institute, University of California, San Diego, 
La Jolla, California 92093, USA, 6Department of Pharmacology, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0654, 
USA and 7Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Email: Choel Kim* - ckim@bcm.edu
* Corresponding author    
Background
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 mecha-
nism 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-kinase anchoring proteins (GKAPs).
To understand the molecular details of PKG dimerization
and targeting to GKAPs, we solved a crystal structure of the
PKG I dimerization/docking domain.
Results
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 I
dimerization, but also reveal the docking surface for
GKAPs.
It is increasingly evident that the fidelity of signal trans-
duction is dependent on the ability of proteins to assem-
ble into pathway specific multiprotein complexes. We
also showed that the surrogate domain of the closely
related cAMP-dependent protein kinase (PKA) forms an
from 4th International Conference of cGMP Generators, Effectors and Therapeutic Implications
Regensburg, Germany. 19–21 June 2009
Published: 11 August 2009
BMC Pharmacology 2009, 9(Suppl 1):P6 doi:10.1186/1471-2210-9-S1-P6
<supplement> <title> <p>4th International Conference of cGMP Generators, Effectors and Therapeutic Implications</p> </title> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1471-2210-9-S1-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2210-9-S1-info.pdf</url> </supplement>
This abstract is available from: http://www.biomedcentral.com/1471-2210/9/S1/P6
© 2009 Casteel et al; licensee BioMed Central Ltd. 
Structures of the Dimerization/Docking domainsFigure 1
Structures of the Dimerization/Docking domains.Page 1 of 2
(page number not for citation purposes)
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X-type helical bundle (Figure 1), providing a completely
different docking surface for binding PKA specific anchor-
ing proteins [1]. The coiled-coil is also a highly important
model system for studying fundamental principles in pro-
tein folding, stability and specificity.
References
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.Page 2 of 2
(page number not for citation purposes)


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

Darren E Casteel

Eric V Smith-Nguyen

Banumathi Sankaran

Glen Spraggon

Eric N Hampton

Renate B Pilz

Susan S Taylor

Choel Kim

Crossref

SS: A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase. Mol Cell

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

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