莫洛尼鼠白血病病毒抑制宿主翻译终止的结构基础。

Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus.

机构信息

Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.

Department of Biochemistry and Molecular Biophysics, Columbia University, HHSC 1310C, 701 West 168th Street, New York, New York 10032, USA.

出版信息

Nat Commun. 2016 Jun 22;7:12070. doi: 10.1038/ncomms12070.

Retroviral reverse transcriptase (RT) of Moloney murine leukemia virus (MoMLV) is expressed in the form of a large Gag-Pol precursor protein by suppression of translational termination in which the maximal efficiency of stop codon read-through depends on the interaction between MoMLV RT and peptidyl release factor 1 (eRF1). Here, we report the crystal structure of MoMLV RT in complex with eRF1. The MoMLV RT interacts with the C-terminal domain of eRF1 via its RNase H domain to sterically occlude the binding of peptidyl release factor 3 (eRF3) to eRF1. Promotion of read-through by MoMLV RNase H prevents nonsense-mediated mRNA decay (NMD) of mRNAs. Comparison of our structure with that of HIV RT explains why HIV RT cannot interact with eRF1. Our results provide a mechanistic view of how MoMLV manipulates the host translation termination machinery for the synthesis of its own proteins.

莫洛尼鼠白血病病毒（MoMLV）的逆转录酶（RT）以大 Gag-Pol 前体蛋白的形式表达，通过抑制翻译终止来实现，其中终止密码子通读的最大效率取决于 MoMLV RT 与肽释放因子 1（eRF1）之间的相互作用。在这里，我们报告了 MoMLV RT 与 eRF1 复合物的晶体结构。MoMLV RT 通过其 RNase H 结构域与 eRF1 的 C 末端结构域相互作用，从而阻碍肽释放因子 3（eRF3）与 eRF1 的结合。MoMLV RNase H 的通读促进作用防止了 mRNA 的无意义介导的 mRNA 降解（NMD）。我们的结构与 HIV RT 的比较解释了为什么 HIV RT 不能与 eRF1 相互作用。我们的结果提供了 MoMLV 如何操纵宿主翻译终止机制来合成自身蛋白的机制观点。