Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: Examination of mutations found in hereditary nonpolyposis colorectal cancer
Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: Examination of mutations found in hereditary nonpolyposis colorectal cancer
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DOI：
10.1128/mcb.18.11.6616
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发表时间：
1998-11-01
影响因子：
5.3
通讯作者：
Fishel, R
中科院分区：
文献类型：
--
作者：
Guerrette, S;Wilson, T;Fishel, R
人类错配修复蛋白hMSH2的突变被发现与遗传性非息肉病性结直肠癌（HNPCC）共分离。以往的生化和物理研究表明，hMSH2与hMSH3和hMSH6形成特异性错对结合复合物。我们通过绘制hMSH2- hMSH3和hMSH2- hmsh6异源二聚体内的接触区域进一步表征了这些蛋白质相互作用。我们证明了hMSH2与hMSH3和hMSH2与hMSH6至少有两个不同的相互作用区域。有趣的是，hMSH2与hMSH3或hMSH6的相互作用区域是相同的，并且这些区域具有协调的线性方向。我们检查了在共识相互作用区域内的HNPCC种类中发现的几种hMSH2错义改变。这些错义突变都没有显示出蛋白质相互作用的缺陷。这些数据支持这样一种观点，即这些与hnpcc相关的突变可能影响异二聚体复合物的一些其他功能，而不仅仅是hMSH2与hMSH3或hMSH2与hMSH6的静态相互作用。
Mutations in the human mismatch repair protein hMSH2 have been found to cosegregate with hereditary nonpolyposis colorectal cancer (HNPCC). Previous biochemical and physical studies have shown that hMSH2 forms specific mispair binding complexes with hMSH3 and hMSH6. We have further characterized these protein interactions by mapping the contact regions within the hMSH2 hMSH3 and the hMSH2-hMSH6 heterodimers. We demonstrate that there are at least two distinct interaction regions of hMSH2 with hMSH3 and hMSH2 with hMSH6. Interestingly, the interaction regions of hMSH2 with either hMSH3 or hMSH6 are identical and there is a coordinated linear orientation of these regions. We examined several missense alterations of hMSH2 found in HNPCC kindreds that are contained within the consensus interaction regions. None of these missense mutations displayed a defect in protein-protein interaction. These data support the notion that these HNPCC-associated mutations may affect some other function of the heterodimeric complexes than simply the static interaction of hMSH2 with hMSH3 or hMSH2 with hMSH6.