X-ray structure and activities of an essential Mononegavirales L-protein domain.
X-ray structure and activities of an essential Mononegavirales L-protein domain.
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DOI：
10.1038/ncomms9749
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发表时间：
2015-11-09
影响因子：
16.6
通讯作者：
Grimes JM
中科院分区：
文献类型：
--
作者：
Paesen GC;Collet A;Sallamand C;Debart F;Vasseur JJ;Canard B;Decroly E;Grimes JM
MononegaVirus的L蛋白具有基因组复制和转录的所有催化活性。它包含六个保守结构域(CR-I至-VI；图1A)。CR-III与聚合酶和聚腺苷酸化活性有关，CR-V与mRNA封顶有关，CR-VI与封端甲基化有关。然而，人们对这些活动是如何编排的知之甚少。在这里，我们介绍了CR-VI+的X射线结构和活性，CR-VI+是人偏肺病毒L的一部分，由CR-VI及其C末端的保守区域+区组成。CR-VI结构域有一个甲基转移酶折叠，除了典型的S-腺苷蛋氨酸结合位点(SAMP)外，还含有一个新的口袋(NSP)，可以容纳核苷。CR-VI缺乏明显的帽子结合位点，而SAMP邻近的含有甲基化核苷酸的位点(SUBP)由于悬垂的+结构域而异常狭窄。Cr-VI+依次甲基化位于2‘O和N7位的CaP，并显示出核苷酸三磷酸酶活性。本文的在线版本(doi：10.1038/ncoms9749)包含补充材料，授权用户可以使用。单重病毒包括埃博拉病毒、狂犬病、麻疹病毒和人类偏肺病毒(HMPV)。在这里，作者报道了hMPV大蛋白结构域的高分辨晶体结构，为该蛋白的mRNA修饰活性提供了洞察力。本文的在线版本(doi：10.1038/ncoms9749)包含补充材料，授权用户可以使用。
The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site (SAMP) also contains a novel pocket (NSP) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the SAMP-adjoining site holding the nucleotides undergoing methylation (SUBP) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2′O and N7 positions, and also displays nucleotide triphosphatase activity. The online version of this article (doi:10.1038/ncomms9749) contains supplementary material, which is available to authorized users. TheMononegaviralesinclude Ebola virus, Rabies, Measles virus and human Metapneumovirus (hMPV). Here, the authors have reported the high resolution crystal structure of a domain of the large protein of hMPV, providing insight into the mRNA modifying activities of this protein. The online version of this article (doi:10.1038/ncomms9749) contains supplementary material, which is available to authorized users.