Structure of the Dom34-Hbs1 complex and implications for no-go decay
Structure of the Dom34-Hbs1 complex and implications for no-go decay
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DOI：
10.1038/nsmb.1922
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发表时间：
2010-10-01
影响因子：
16.8
通讯作者：
Song, Haiwei
中科院分区：
文献类型：
--
作者：
Chen, Liming;Muhlrad, Denise;Song, Haiwei
在一个涉及Dom34和Hbs1蛋白的过程中，No-go衰变（NGD）靶向翻译延伸中断的mrna进行内核溶解裂解。Schizosaccharomyces pombe Dom34-Hbs1复合物的晶体结构显示出与eRF1-eRF3-GTP和EF-Tu-tRNA-GDPNP相似的整体形状。与eRF1和GTP结合eRF3类似，Dom34和GTP结合Hbs1具有很强的协同性，Dom34作为GTP解离抑制剂（GDI）。在与Hbs1结合时，Dom34发生了显著的构象变化，导致Dom34类似于tRNA的一部分，并将一个保守的基本区域定位在肽基转移酶中心附近的位置。这些结果支持了Dom34-Hbs1复合体的功能，即终止翻译，从而将mrna提交给NGD。与这一作用一致的是，精氨酸密码子序列的NGD与Dom34-Hbs1复合物无关，而精氨酸密码子对延伸有很强的阻断作用。
No-go decay (NGD) targets mRNAs with stalls in translation elongation for endonucleolytic cleavage in a process involving the Dom34 and Hbs1 proteins. The crystal structure of a Schizosaccharomyces pombe Dom34-Hbs1 complex reveals an overall shape similar to that of eRF1-eRF3-GTP and EF-Tu-tRNA-GDPNP. Similarly to eRF1 and GTP binding to eRF3, Dom34 and GTP bind to Hbs1 with strong cooperativity, and Dom34 acts as a GTP-dissociation inhibitor (GDI). A marked conformational change in Dom34 occurs upon binding to Hbs1, leading Dom34 to resemble a portion of a tRNA and to position a conserved basic region in a position expected to be near the peptidyl transferase center. These results support the idea that the Dom34-Hbs1 complex functions to terminate translation and thereby commit mRNAs to NGD. Consistent with this role, NGD at runs of arginine codons, which cause a strong block to elongation, is independent of the Dom34-Hbs1 complex.