Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid.
Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid.
复制标题
DOI：
10.1371/journal.ppat.1005981
复制
发表时间：
2016-11
期刊：
影响因子：
6.7
通讯作者：
Taylor IA
中科院分区：
文献类型：
--
作者：
Ball NJ;Nicastro G;Dutta M;Pollard DJ;Goldstone DC;Sanz-Ramos M;Ramos A;Müllers E;Stirnnagel K;Stanke N;Lindemann D;Stoye JP;Taylor WR;Rosenthal PB;Taylor IA
泡沫逆转录病毒亚科（Spumaretrovirinae）或泡沫病毒（FVs）是感染许多种类的猴和猿的复杂逆转录病毒。尽管序列同源性很小，但FV和正逆转录病毒Gag蛋白执行等同的功能，包括基因组包装、病毒体组装、运输和膜靶向。然而，缺乏FV的结构信息，并且不清楚不同的FV和正逆转录病毒Gag分子如何共享相同的功能。为了探测FV和正逆转录病毒Gag的功能重叠，我们已经确定了来自原型FV（PFV）的Gag的中心区域的结构。该结构包括两个全α螺旋结构域NtDCEN和CtDCEN，尽管它们没有序列相似性，但我们表明它们与原型正逆转录病毒衣壳蛋白（CA）的N-（NtDCA）和C-末端结构域（CtDCA）共享相同的核心折叠。此外，与正逆转录病毒CA的结构比较将PFV NtDCEN和CtDCEN分别与NtDCA和CtDCA对齐。进一步的体外和功能性病毒学测定揭示，进行结构域间NtDCEN-CtDCEN相互作用的残基是PFV衣壳组装所需的，并且完整的衣壳是PFV逆转录所需的。这些数据提供了第一个信息，涉及的Gag蛋白的Spuma和Orthoretrovirinae，并建议一个共同的祖先，这两个谱系包含一个古老的CA折叠。泡沫病毒（FV）或泡沫逆转录病毒的名称来源于它们在细胞培养中引起的细胞病变效应。然而，人类的感染是良性的，并且FV已经通过来自猿的人畜共患病进入人群，导致原型FV（PFV）的出现。与所有逆转录病毒一样，FV含有gag、pol和env结构基因，并通过逆转录和宿主基因组整合进行复制。Gag是主要的结构蛋白，是基因组包装、病毒体组装、运输和外出所必需的。然而，尽管功能上等同，但FV和正逆转录病毒Gag几乎没有序列同源性，并且不清楚它们如何执行相同的功能。因此，为了了解更多关于FV和正逆转录病毒复制之间的关系，我们进行了PFV-Gag的结构研究。在这里，我们提出了从中央区域PFV-Gag的CA域的结构，并表明，尽管很少的序列相似性，他们共享相同的折叠作为CA域的正逆转录病毒Gag。这些数据提供了与Spuma和正逆转录病毒亚科Gag蛋白相关的第一个信息。我们讨论了我们的研究结果在进化的分歧spuma和orthotroviral谱系。
The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information for FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. To probe the functional overlap of FV and orthoretroviral Gag we have determined the structure of a central region of Gag from the Prototype FV (PFV). The structure comprises two all α-helical domains NtDCEN and CtDCEN that although they have no sequence similarity, we show they share the same core fold as the N- (NtDCA) and C-terminal domains (CtDCA) of archetypal orthoretroviral capsid protein (CA). Moreover, structural comparisons with orthoretroviral CA align PFV NtDCEN and CtDCEN with NtDCA and CtDCA respectively. Further in vitro and functional virological assays reveal that residues making inter-domain NtDCEN—CtDCEN interactions are required for PFV capsid assembly and that intact capsid is required for PFV reverse transcription. These data provide the first information that relates the Gag proteins of Spuma and Orthoretrovirinae and suggests a common ancestor for both lineages containing an ancient CA fold. Foamyviruses (FVs) or Spuma-retroviruses derive their name from the cytopathic effects they cause in cell culture. However, infection in humans is benign and FVs have entered the human population through zoonosis from apes resulting in the emergence of Prototype FV (PFV). Like all retroviruses, FVs contain gag, pol and env structural genes and replicate through reverse-transcription and host genome integration. Gag, the major structural protein, is required for genome packaging, virion assembly, trafficking and egress. However, although functionally equivalent, FV and orthoretroviral Gag share little sequence homology and it is unclear how they perform the same function. Therefore, to understand more about relationship between FV and orthoretroviral replication we have carried out structural studies of PFV-Gag. Here we present the structure of CA domains from a central region PFV-Gag and show that despite little sequence similarity they share the same fold as the CA domains of orthoretroviral Gag. These data provide the first information relating the Spuma and Orthoretrovirinae Gag proteins. We discuss our findings in terms of evolutionary divergence of spuma and orthoretroviral lineages.
登录
查看更多内容
影响因子：
64.8
作者：
Bharat, Tanmay A. M.;Davey, Norman E.;Briggs, John A. G.
通讯作者：
Briggs, John A. G.
影响因子：
5.3
作者：
DUBRIDGE, RB;TANG, P;CALOS, MP
通讯作者：
CALOS, MP
影响因子：
2.7
作者：
BARTELS, C;XIA, TH;WUTHRICH, K
通讯作者：
WUTHRICH, K
DOI：
10.1073/pnas.1013426108
发表时间：
2011-01-11
影响因子：
11.1
作者：
Ganser-Pornillos, Barbie K.;Chandrasekaran, Viswanathan;Yeager, Mark
通讯作者：
Yeager, Mark
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A