一种使A激酶锚定蛋白（AKAP）与环磷酸腺苷（cAMP）依赖性蛋白激酶的RII亚型结合的动态机制。
A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase.
作者信息
Kinderman Francis S, Kim Choel, von Daake Sventja, Ma Yuliang, Pham Bao Q, Spraggon Glen, Xuong Nguyen-Huu, Jennings Patricia A, Taylor Susan S
机构信息
Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, California 92093, USA.
出版信息
Mol Cell. 2006 Nov 3;24(3):397-408. doi: 10.1016/j.molcel.2006.09.015.
A kinase-anchoring proteins (AKAPs) target PKA to specific microdomains by using an amphipathic helix that docks to N-terminal dimerization and docking (D/D) domains of PKA regulatory (R) subunits. To understand specificity, we solved the crystal structure of the helical motif from D-AKAP2, a dual-specific AKAP, bound to the RIIalpha D/D domain. The 1.6 Angstrom structure reveals how this dynamic, hydrophobic docking site is assembled. A stable, hydrophobic docking groove is formed by the helical interface of two RIIalpha protomers. The flexible N terminus of one protomer is then recruited to the site, anchored to the peptide through two essential isoleucines. The other N terminus is disordered. This asymmetry provides greater possibilities for AKAP docking. Although there is strong discrimination against RIalpha in the N terminus of the AKAP helix, the hydrophobic groove discriminates against RIIalpha. RIalpha, with a cavity in the groove, can accept a bulky tryptophan, whereas RIIalpha requires valine.
一种激酶锚定蛋白（AKAPs）通过利用一个两亲性螺旋将蛋白激酶A（PKA）靶向特定的微结构域，该螺旋与PKA调节（R）亚基的N端二聚化和对接（D/D）结构域对接。为了理解特异性，我们解析了来自双特异性AKAP（D-AKAP2）的螺旋基序与RIIα D/D结构域结合的晶体结构。1.6埃的结构揭示了这个动态的疏水对接位点是如何组装的。一个稳定的疏水对接凹槽由两个RIIα原体的螺旋界面形成。然后，一个原体的柔性N端被招募到该位点，通过两个必需的异亮氨酸锚定在肽上。另一个N端是无序的。这种不对称性为AKAP对接提供了更多可能性。尽管在AKAP螺旋的N端对RIα有强烈的排斥，但疏水凹槽对RIIα有排斥作用。RIα在凹槽中有一个腔，可以容纳一个大的色氨酸，而RIIα则需要缬氨酸。
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