A novel mechanism of PKA anchoring revealed by solution structures of anchoring complexes
A novel mechanism of PKA anchoring revealed by solution structures of anchoring complexes
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DOI：
10.1093/emboj/20.7.1651
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发表时间：
2001-04-02
期刊：
影响因子：
11.4
通讯作者：
Jennings, PA
中科院分区：
文献类型：
--
作者：
Newlon, MG;Roy, M;Jennings, PA
细胞内信号事件的特异性部分地由蛋白激酶和磷酸酶的区室化控制。这些酶的亚细胞定位通常由蛋白-蛋白相互作用维持。一个典型的例子是cAMP依赖性蛋白激酶（PKA）通过其与A-激酶锚定蛋白（AKAP）的结合而区室化。位于每个调节（R）亚基原体的前45个残基内的对接和二聚化结构域（D/D）形成其锚定配偶体的高亲和力结合位点。本文报道了用溶液NMR方法得到的两个D/D-AKAP肽复合物的结构，一个与Ht 31（493-515），另一个与AKAP 79（392-413），我们给出了第一个直接的结构数据，证明了肽的螺旋性质，结构揭示了螺旋AKAP肽和PKA R亚基上保守的疏水相互作用表面，其负责介导复合物中的高亲和力缔合。与其他X型四螺旋束二聚体蛋白中所见的二聚体-二聚体相互作用不同，我们的结构揭示了一种新的疏水凹槽，可容纳每个RII α D/D的一个AKAP。
The specificity of intracellular signaling events is controlled, in part, by compartmentalization of protein kinases and phosphatases, The subcellular localization of these enzymes is often maintained by protein-protein interactions. A prototypic example is the compartmentalization of the cAMP-dependent protein kinase (PKA) through its association with A-kinase anchoring proteins (AKAPs), A docking and dimerization domain (D/D) located within the first 45 residues of each regulatory (R) subunit protomer forms a high affinity binding site for its anchoring partner. We now report the structures of two D/D-AKAP peptide complexes obtained by solution NMR methods, one with Ht31(493-515) and the other with AKAP79(392-413), We present the first direct structural data demonstrating the helical nature of the peptides, The structures reveal conserved hydrophobic interaction surfaces on the helical AKAP peptides and the PKA R subunit, which are responsible for mediating the high affinity association in the complexes. In a departure from the dimer-dimer interactions seen in other X-type four-helix bundle dimeric proteins, our structures reveal a novel hydrophobic groove that accommodates one AKAP per RII alpha D/D.