Structural highlights
Publication Abstract from PubMedMembrane-bound cGMP-dependent protein kinase (PKG) II is a key regulator of bone growth, renin secretion, and memory formation. Despite its crucial physiological roles, little is known about its cyclic nucleotide selectivity mechanism due to a lack of structural information. Here, we find that the C-terminal cyclic nucleotide binding (CNB-B) domain of PKG II binds cGMP with higher affinity and selectivity, compared to its N-terminal CNB (CNB-A) domain. To understand the structural basis of cGMP selectivity, we solved co-crystal structures of the CNB domains with cyclic nucleotides. Our structures combined with mutagenesis demonstrate that the guanine specific contacts at D412 and R415 of the alphaC-helix of CNB-B are crucial for cGMP selectivity and activation of PKG II. Structural comparison with the cGMP selective CNB domains of human PKG I and Plasmodium falciparum PKG (PfPKG) shows different contacts with the guanine moiety, revealing a unique cGMP selectivity mechanism for PKG II. Structural Basis of Cyclic Nucleotide Selectivity in cGMP-Dependent Protein Kinase II.,Campbell JC, Kim JJ, Li KY, Huang GY, Reger AS, Matsuda S, Sankaran B, Link TM, Yuasa K, Ladbury JE, Casteel DE, Kim C J Biol Chem. 2016 Jan 14. pii: jbc.M115.691303. PMID:26769964[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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