SARS-CoV-2 NSP12 associates with the TRiC complex and the P323L substitution is a host adaption
SARS-CoV-2 NSP12 associates with the TRiC complex and the P323L substitution is a host adaption
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DOI：
10.1101/2023.03.18.533280
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
Muhannad Alruwaili;S. Armstrong;T. Prince;Maximilian Erdmann;D. Matthews;A. Davidson;Waleed Aljabr;J. Hiscox
中科院分区：
文献类型：
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作者：
Muhannad Alruwaili;S. Armstrong;T. Prince;Maximilian Erdmann;D. Matthews;A. Davidson;Waleed Aljabr;J. Hiscox
SARS-CoV-2于2019年底出现在人群中，人际传播主导了进化格局，并推动了不同谱系的选择。第一个导致传输增加的主要变化是刺突蛋白中的D 614 G取代。这伴随着病毒RNA依赖性RNA聚合酶（RdRp）（NSP 12）中的P323 L取代。与D 614 G一起，这些变化是全球主要SARS-CoV-2格局的根源。在这里，我们发现NSP 12与细胞蛋白质形成相互作用组。NSP 12的功能依赖于T-复合物蛋白环复合物，一种分子伴侣。相反，NSP 12变体与磷酸酶复合物的组分（PP 2/PP 2A和STRN 3）之间存在差异关联。表达NSP 12 L323的病毒对PP 2A中的扰动较不敏感，并支持了SARS-CoV-2在人类中正在进行的基因型到表型适应并不完全限于刺突蛋白的范例.
SARS-CoV-2 emerged into the human population in late 2019 and human to human transmission has dominated the evolutionary landscape and driven the selection of different lineages. The first major change that resulted in increased transmission was the D614G substitution in the spike protein. This was accompanied by the P323L substitution in the viral RNA dependent RNA polymerase (RdRp) (NSP12). Together, with D614G these changes are the root of the predominant global SARS-CoV-2 landscape. Here, we found that NSP12 formed an interactome with cellular proteins. The functioning of NSP12 was dependent on the T-complex protein Ring Complex, a molecular chaperone. In contrast, there was differential association between NSP12 variants and components of a phosphatase complex (PP2/PP2A and STRN3). Virus expressing NSP12L323 was less sensitive to perturbations in PP2A and supports the paradigm that ongoing genotype to phenotype adaptation of SARS- CoV-2 in humans is not exclusively restricted to the spike protein.