P. Banky et al., Isoform-specific differences between the type I alpha and II alpha cyclic AMP-dependent protein kinase anchoring domains revealed by solution NMR, J BIOL CHEM, 275(45), 2000, pp. 35146-35152
Cyclic AMP dependent protein kinase (PKA) is controlled, in part, by the su
bcellular localization of the enzyme (1). Discovery of dual Specificity anc
horing 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 loca
lized in a novel, dynamic fashion as opposed to the apparent static localiz
ation of the type II enzyme. Recently, the structure of the dimerization/do
cking (D/D) domain from the type II enzyme was solved (3), This work reveal
ed an X-type four-helix bundle motif with a hydrophobic patch that modulate
s AKAP interactions. To understand the dynamic versus static localization o
f PKA, multidimensional NMR techniques were used to investigate the structu
ral features of the type I D/D domain. Our results indicate a conserved hel
ix-turn-helix motif in the type I and type II D/D domains. However, importa
nt differences between the two-domains are evident in the extreme NH2 termi
nus: this region is extended in the type II domain, whereas it is helical i
n the type I protein. The NH2-terminal residues in RII alpha contain determ
inants for anchoring, and the orientation and packing of this helical eleme
nt in the RI alpha structure may have profound consequences in:the recognit
ion surface presented to the AKAPs.