Analysis of the retrovirus capsid interdomain linker region
Analysis of the retrovirus capsid interdomain linker region
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DOI：
10.1016/s0042-6822(02)00142-3
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发表时间：
2003-03-30
期刊：
影响因子：
3.7
通讯作者：
Barklis, E
中科院分区：
文献类型：
--
作者：
Arvidson, B;Seeds, J;Barklis, E
在结构研究中，逆转录病毒衣壳结构域间连接区已被证明是CA N-末端结构域和其C-末端结构域之间的柔性连接体。为了分析接头区的功能，我们在全长M-MuLV结构前体蛋白（PrGag）的背景下，研究了三种莫洛尼鼠白血病病毒（M-MuLV）衣壳接头突变/变异在体内的影响。两个突变A1 SP和A5 SP分别在接头区域内插入了三个和七个额外的密码子，以测试接头长度增加的影响。第三种变体HIV/Mo代表嵌合HIV-1/M-MuLV PrGag蛋白，在接头区融合。当在细胞中表达时，这三种变体降低了病毒颗粒组装的效率，PrGag蛋白和颗粒在细胞质膜上积累。尽管病毒RNA的PrGag识别没有受损，但衣壳接头变体颗粒异常，稳定性降低、密度异常以及异常的多叶和管状形态。此外，而不是交联的PrGag二聚体，颗粒相关的A1 SP，A5 SP，和HIV/Mo蛋白显示出增加的倾向交联的三聚体。我们的研究结果表明，一个野生型逆转录病毒衣壳连接区是必要的衣壳蛋白结构域的正确对齐。(C)2003 Elsevier Science（美国）。All rights reserved.
In structural studies, the retrovirus capsid interdomain linker region has been shown as a flexible connector between the CA N-terminal domain and its C-terminal domain. To analyze the function of the linker region, we have examined the effects of three Moloney murine leukemia virus (M-MuLV) capsid linker mutations/variations in vivo, in the context of the full-length M-MuLV structural precursor protein (PrGag). Two mutations, A1SP and A5SP, respectively, inserted three and seven additional codons within the linker region to test the effects of increased linker lengths. The third variant, HIV/Mo, represented a chimeric HIV-1/M-MuLV PrGag protein, fused at the linker region. When expressed in cells, the three variants reduced the efficiency of virus particle assembly, with PrGag proteins and particles accumulating at the cellular plasma membranes. Although PrGag recognition of viral RNA was not impaired, the capsid linker variant particles were abnormal, with decreased stabilities, anomalous densities, and aberrant multiple lobed and tubular morphologies. Additionally, rather than crosslinking as PrGag dimers, particle-associated A1SP, A5SP, and HIV/Mo proteins showed an increased propensity to crosslink as trimers. Our results suggest that a wild-type retrovirus capsid linker region is required for the proper alignment of capsid protein domains. (C) 2003 Elsevier Science (USA). All rights reserved.