Launer-Felty Katherine, Wong C Jason, Cole James L
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut.
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut; Department of Chemistry, University of Connecticut, Storrs, Connecticut.
Biophys J. 2015 Feb 3;108(3):748-57. doi: 10.1016/j.bpj.2014.12.014.
Protein kinase R (PKR) is activated by dsRNA produced during virus replication and plays a major role in the innate immunity response to virus infection. In response, viruses have evolved multiple strategies to evade PKR. Adenovirus virus-associated RNA-I (VAI) is a short, noncoding transcript that functions as an RNA decoy to sequester PKR in an inactive state. VAI consists of an apical stem-loop, a highly structured central domain, and a terminal stem. Chemical probing and mutagenesis demonstrate that the central domain is stabilized by a pseudoknot. A structural model of VAI was obtained from constraints derived from chemical probing and small angle x-ray scattering (SAXS) measurements. VAI adopts a flat, extended conformation with the apical and terminal stems emanating from a protuberance in the center. This model reveals how the apical stem and central domain assemble to produce an extended duplex that is precisely tuned to bind a single PKR monomer with high affinity, thereby inhibiting activation of PKR by viral dsRNA.
蛋白激酶R（PKR）由病毒复制过程中产生的双链RNA激活，在对病毒感染的先天免疫反应中起主要作用。作为回应，病毒已经进化出多种策略来逃避PKR。腺病毒相关RNA-I（VAI）是一种短的非编码转录本，作为一种RNA诱饵，将PKR隔离在非活性状态。VAI由一个顶端茎环、一个高度结构化的中央结构域和一个末端茎组成。化学探针和诱变表明，中央结构域由一个假结稳定。VAI的结构模型是从化学探针和小角X射线散射（SAXS）测量得出的限制条件中获得的。VAI采用扁平、延伸的构象，顶端和末端茎从中心的一个突出部分伸出。该模型揭示了顶端茎和中央结构域如何组装以产生一个延伸的双链体，该双链体经过精确调整以高亲和力结合单个PKR单体，从而抑制病毒双链RNA对PKR的激活。
