The N terminus of Saccharomyces cerevisiale Msh6 is an unstructured tether to PCNA
The N terminus of Saccharomyces cerevisiale Msh6 is an unstructured tether to PCNA
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DOI：
10.1016/j.molcel.2007.04.024
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发表时间：
2007-05-25
期刊：
影响因子：
16
通讯作者：
Kolodner, Richard D.
中科院分区：
文献类型：
--
作者：
Shell, Scarlet S.;Putnam, Christopher D.;Kolodner, Richard D.
真核MutS同源复合物Msh 2-Msh 6和Msh 2-Msh 3在错配修复（MMR）期间识别DNA中的错配碱基。Msh 6和Msh 3的真核生物特异性N-末端区域（NTR）除了通过证明它们含有N-末端PCNA相互作用基序之外还没有被表征。在这里，我们已经证明了遗传Msh 6的NTR在MMR中具有重要作用，这与PCNA结合部分冗余。小角X射线散射（SAXS）被用来确定与Msh 2-Msh 6和与分离的Msh 6 NTR的PCNA的复合物的溶液结构，揭示了Msh 6 NTR是一个天然的无序域，形成了Msh 6和PCNA之间的延伸系链。此外，计算分析的PCNA相互作用基序在S。酿酒酵母蛋白质组的研究表明，柔性接头是PCNA相互作用蛋白质的共同主题，其可以用于定位这些结合伴侣而不将它们严格限制在PCNA的紧邻区域。
The eukaryotic MutS homolog complexes, Msh2-Msh6 and Msh2-Msh3, recognize mismatched bases in DNA during mismatch repair (MMR). The eukaryote-specific N-terminal regions (NTRs) of Msh6 and Msh3 have not been characterized other than by demonstrating that they contain an N-terminal PCNA-interacting motif. Here we have demonstrated genetically that the NTR of Msh6 has an important role in MMR that is partially redundant with PCNA binding. Small-angle X-ray scattering (SAXS) was used to determine the solution structure of the complex of PCNA with Msh2-Msh6 and with the isolated Msh6 NTR, revealing that the Msh6 NTR is a natively disordered domain that forms an extended tether between Msh6 and PCNA. Moreover, computational analysis of PCNA-interacting motifs in the S. cerevisiae proteome indicated that flexible linkers are a common theme for PCNA-interacting proteins that may serve to localize these binding partners without tightly restraining them to the immediate vicinity of PCNA.