A network of allosterically coupled residues in the bacteriophage T4 Mre11-Rad50 complex
A network of allosterically coupled residues in the bacteriophage T4 Mre11-Rad50 complex
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DOI：
10.1002/pro.3028
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发表时间：
2016-11-01
期刊：
影响因子：
8
通讯作者：
Nelson, Scott W.
中科院分区：
文献类型：
--
作者：
Gao, Yang;Meyer, Jennifer R.;Nelson, Scott W.
Mre11-Rad50 （MR）蛋白复合物，分别由核酸酶和atp酶组成，参与双链断裂的加工，作为其修复的复杂机制的一部分。虽然很清楚MR复合物受变构调节，并且在核酸酶和atp酶活性位点之间存在通信，但其潜在机制尚不清楚。我们对Mre11和Rad50进行了统计耦合分析，根据它们的进化相关性预测了它们的连锁残基。这一分析预测了六个残基可能是变构耦合的共同进化扇区。利用核酸酶和atp酶活性的双突变周期分析对预测结果进行了验证。结果表明，位于Mre11活性位点附近的酪氨酸残基与位于40埃以上的Rad50残基发生变构偶联。这种变构偶联可能是该复合物中atp酶和核酸酶活性相互调节的基础。
The Mre11-Rad50 (MR) protein complex, made up of a nuclease and ATPase, respectively, is involved in the processing of double-strand breaks as part of an intricate mechanism for their repair. Although it is clear that the MR complex is subject to allosteric regulation and that there is communication between the nuclease and ATPase active sites, the underlying mechanisms are poorly understood. We performed statistical coupling analysis on Mre11 and Rad50 to predict linked residues based on their evolutionary correlation. This analysis predicted a coevolving sector of six residues that may be allosterically coupled. The prediction was tested using double-mutant cycle analysis of nuclease and ATPase activity. The results indicate that a tyrosine residue located near the active site of Mre11 is allosterically coupled to several Rad50 residues located over 40 angstrom away. This allosteric coupling may be the basis for the reciprocal regulation of the ATPase and nuclease activities of the complex.