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Solution Conformation of Bovine Leukemia Virus Gag Suggests an Elongated Structure

机译:牛白血病病毒GAG的溶液构象表明细长结构

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Bovine leukemia virus (BLV) is a deltaretrovirus that infects domestic cattle. The structural protein Gag, found in all retroviruses, is a polyprotein comprising three major functional domains: matrix (MA), capsid (CA), and nucleocapsid (NC). Previous studies have shown that both mature BLV MA and NC are able to bind to nucleic acids; however, the viral assembly process and packaging of viral genomic RNA requires full-length Gag to produce infectious particles. Compared to lentiviruses, little is known about the structure of the Gag polyprotein of deltaretroviruses. In this work, structural models of full-length BLV Gag and Gag lacking the MA domain were generated based on previous structural data of individual domains, homology modeling, and flexible fitting to SAXS data using molecular dynamics. The models were used in molecular dynamic simulations to determine the relative mobility of the protein backbone. Functional annealing assays revealed the role of MA in the nucleic acid chaperone activity of BLV Gag. Our results show that full-length BLV Gag has an elongated rod-shaped structure that is relatively rigid, with the exception of the linker between the MA and CA domains. Deletion of the MA domain maintains the elongated structure but alters the rate of BLV Gag-facilitated annealing of two complementary nucleic acids. These data are consistent with a role for the MA domain of retroviral Gag proteins in modulating nucleic acid binding and chaperone activity.
机译:牛白血病病毒(BLV)是一种感染国内牛的Deltaretrovirus。在所有逆转录病毒中发现的结构蛋白堵塞是包含三个主要功能域:基质(MA),衣壳(CA)和核衣壳(NC)的聚丙烯蛋白。以前的研究表明,成熟的BLV MA和NC都能够与核酸结合;然而,病毒组装工艺和病毒基因组RNA的包装需要全长GAG以产生感染性颗粒。与慢病毒相比,关于Deltaretroviruses的Gag Polyprotein的结构很少。在这项工作中,基于使用分子动力学的各个域,同源性建模和柔性拟合的先前结构数据,生成全长BLV Gag和缺乏MA域的GAG的结构模型。该模型用于分子动态模拟以确定蛋白质骨干的相对迁移率。功能性退火测定揭示了MA在BLV胶原的核酸伴随活性中的作用。我们的结果表明,全长BLV GAG具有细长的杆状结构,其相对刚性,除了MA和Ca结构域之间的接头。 MA域的缺失保持细长结构,但改变了两个互补核酸的BLV Gag促进退火的速率。这些数据与调节核酸结合和伴侣活性的逆转录病毒GAG蛋白的MA结构域的作用一致。

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