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首页> 外文期刊>Molecular and Cellular Biology >Requirement of PKR Dimerization Mediated by Specific Hydrophobic Residues for Its Activation by Double-Stranded RNA and Its Antigrowth Effects in Yeast
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Requirement of PKR Dimerization Mediated by Specific Hydrophobic Residues for Its Activation by Double-Stranded RNA and Its Antigrowth Effects in Yeast

机译：特定疏水残基介导的PKR二聚体对双链RNA活化及其在酵母中的抗生长作用的要求

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摘要

The roles of protein dimerization and double-stranded RNA (dsRNA) binding in the biochemical and cellular activities of PKR, the dsRNA-dependent protein kinase, were investigated. We have previously shown that both properties of the protein are mediated by the same domain. Here we show that dimerization is mediated by hydrophobic residues present on one side of an amphipathic α-helical structure within this domain. Appropriate substitution mutations of residues on that side produced mutants with increased or decreased dimerization activities. Using these mutants, we demonstrated that dimerization is not essential for dsRNA binding. However, enhancing dimerization artificially, by providing an extraneous dimerization domain, increased dsRNA binding of both wild-type and mutant proteins. In vitro, the dimerization-defective mutants could not be activated by dsRNA but were activated normally by heparin. In Saccharomyces cerevisiae, unlike wild-type PKR, these mutants could not inhibit cell growth and the dsRNA-binding domain of the dimerization-defective mutants could not prevent the antigrowth effect of wild-type PKR. These results demonstrate the biological importance of the dimerization properties of PKR.
机译：研究了蛋白质二聚化和双链RNA（dsRNA）结合在dsRNA依赖性蛋白激酶PKR的生化和细胞活性中的作用。先前我们已经表明，蛋白质的两个特性都由相同的结构域介导。在这里，我们显示二聚化是由该域内两亲性α-螺旋结构一侧的疏水残基介导的。该侧残基的适当取代突变产生具有增加或减少的二聚化活性的突变体。使用这些突变体，我们证明了二聚化对于dsRNA结合不是必需的。但是，通过提供外部二聚结构域，人为地增强了二聚化，从而提高了野生型和突变型蛋白质的dsRNA结合。在体外，二聚化缺陷型突变体不能被dsRNA激活，但可以被肝素正常激活。在酿酒酵母中，与野生型PKR不同，这些突变体不能抑制细胞生长，而二聚化缺陷型突变体的dsRNA结合结构域则不能阻止野生型PKR的抗生长作用。这些结果证明了PKR的二聚性质的生物学重要性。

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