Structural basis of cyclic nucleotide selectivity in cGMP dependent protein kinase II

• Published in: BMC pharmacology & toxicology Vol. 16; no. S1; p. A15
• Main Authors: Campbell, James C., Li, Kevin Y., Kim, Jeong Joo, Huang, Gilbert, Reger, Albert S., Matsuda, Shinya, Sankaran, Banumathi, Link, Todd M., Yuasa, Keizo, Ladbury, John E., Kim, Choel
• Format: Journal Article
• Language: English
• Published: United States BioMed Central 02-09-2015
• Subjects: BASIC BIOLOGICAL SCIENCES; Meeting Abstract
• ISSN: 2050-6511; 2050-6511
• DOI: 10.1186/2050-6511-16-S1-A15

As a central mediator of the natriuretic peptide-cGMP signalling cascade, membrane bound type II cGMP dependent protein kinase (PKG II) is a key regulator of bone growth, renin secretion, and memory formation. It represents an important drug target for treating osteoporosis, cystic fibrosis, and memory loss [1-5]. In spite of its crucial physiological roles and its importance as a therapeutic target, little is known about its mechanisms of cyclic nucleotide selectivity and activation due to a lack of structural information. PKG II contains an Nterminal regulatory (R)-domain that binds a C-terminal catalytic (C)-domain in the absence of cGMP. Binding of cGMP to the cyclic nucleotide binding domains (CNB-A and B) within the R-domain releases the C-domain, leading to activation. We sought to understand the cyclic nucleotide selectivity and activation mechanisms of PKG II by studying each CNB domain.