Allosteric cooperativity in protein kinase A
Allosteric cooperativity in protein kinase A
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DOI：
10.1073/pnas.0709214104
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发表时间：
2008-01-15
影响因子：
11.1
通讯作者：
Veglia, Gianluigi
中科院分区：
文献类型：
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作者：
Masterson, Larry R.;Mascioni, Alessandro;Veglia, Gianluigi
蛋白质中的变构信号需要由高度保守的残基介导的远程通讯，这种通讯通常是由配体结合触发的。在这篇文章中，我们用核磁共振波谱绘制了蛋白激酶A催化亚基中的变构网络。我们发现，正变构协作性是由核苷酸和底物通过主要构象状态：载脂蛋白、中间态和闭合态的转变而产生的。变构网络被一个单点突变(Y204A)破坏，这也使配体结合的协同性解偶联。因为蛋白激酶A是整个基因组的原型，所以这些发现可以作为描述其他蛋白激酶长程偶联的范例。
Allosteric signaling in proteins requires long-range communication mediated by highly conserved residues, often triggered by ligand binding. In this article, we map the allosteric network in the catalytic subunit of protein kinase A using NMR spectroscopy. We show that positive allosteric cooperativity is generated by nucleotide and substrate binding during the transitions through the major conformational states: apo, intermediate, and closed. The allosteric network is disrupted by a single site mutation (Y204A), which also decouples the cooperativity of ligand binding. Because protein kinase A is the prototype for the entire kinome, these findings may serve as a paradigm for describing long-range coupling in other protein kinases.