Isoform-specific Differences between the Type Iα and IIα Cyclic AMP-dependent Protein Kinase Anchoring Domains Revealed by Solution NMR

Cyclic AMP dependent protein kinase (PKA) is controlled, in part, by the subcellular localization of the enzyme (1). Discovery of dual specificityanchoring proteins(d-AKAPs) indicates that not only is the type II, but also the type I, enzyme localized (2). It appears that the type I enzyme is locali...

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Published in:The Journal of biological chemistry 2000-11, Vol.275 (45), p.35146-35152
Main Authors: Banky, Poopak, Newlon, Marceen G., Roy, Melinda, Garrod, Siv, Taylor, Susan S., Jennings, Patricia A.
Format: Article
Language:English
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Summary:Cyclic AMP dependent protein kinase (PKA) is controlled, in part, by the subcellular localization of the enzyme (1). Discovery of dual specificityanchoring proteins(d-AKAPs) indicates that not only is the type II, but also the type I, enzyme localized (2). It appears that the type I enzyme is localized in a novel, dynamic fashion as opposed to the apparent static localization of the type II enzyme. Recently, the structure of the dimerization/docking (D/D) domain from the type II enzyme was solved (3). This work revealed an X-type four-helix bundle motif with a hydrophobic patch that modulates AKAP interactions. To understand the dynamic versus static localization of PKA, multidimensional NMR techniques were used to investigate the structural features of the type I D/D domain. Our results indicate a conserved helix-turn-helix motif in the type I and type II D/D domains. However, important differences between the two domains are evident in the extreme NH2 terminus: this region is extended in the type II domain, whereas it is helical in the type I protein. The NH2-terminal residues in RIIα contain determinants for anchoring, and the orientation and packing of this helical element in the RIα structure may have profound consequences in the recognition surface presented to the AKAPs.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M003961200