Background

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 mechan-isms of cyclic nucleotide selectivity and activation due to a lack of structural information. PKG II contains an N-terminal regulatory (R)-domain that binds a C-termina