Conserved and Variable Features of Gag Structure and Arrangement in Immature Retrovirus Particles
Conserved and Variable Features of Gag Structure and Arrangement in Immature Retrovirus Particles
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DOI：
10.1128/jvi.01423-10
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发表时间：
2010-11-01
影响因子：
5.4
通讯作者：
Briggs, John A. G.
中科院分区：
文献类型：
--
作者：
de Marco, Alex;Davey, Norman E.;Briggs, John A. G.
逆转录病毒的组装是由Gag多蛋白的寡聚化驱动的。我们已经使用冷冻电子断层扫描与subtomogram平均来描述在体外组装的Gag颗粒从人类免疫缺陷病毒，梅森-辉瑞猴病毒，劳斯肉瘤病毒的三维结构。它们代表三种不同的逆转录病毒属：慢病毒、β逆转录病毒和α逆转录病毒。这三种结构的比较揭示了Gag的超分子组织的特征，这些特征在属之间是保守的，因此反映了Gag-Gag相互作用的一般原则和特定于某些属的特征。所有三种Gag蛋白组装形成具有不规则缺陷的近似球形六聚体晶格。在所有三个属中，CA的N-末端结构域排列在大孔周围的六聚体环中。在环相遇的地方，分配给CA的C-末端结构域的2倍密度在相邻环之间延伸，并在6倍对称轴处以一定密度连接在一起，该密度朝向颗粒的中心延伸到核酸层中。尽管这种一般排列是保守的，但在整个CA和间隔肽区域可以看到差异。这些差异可能与属间的序列差异有关。我们的结论是，CA的结构域的安排是很好的跨属保守，而CA之间的关系，间隔肽区域，和核酸是更具体的每一个属。
The assembly of retroviruses is driven by oligomerization of the Gag polyprotein. We have used cryo-electron tomography together with subtomogram averaging to describe the three-dimensional structure of in vitro-assembled Gag particles from human immunodeficiency virus, Mason-Pfizer monkey virus, and Rous sarcoma virus. These represent three different retroviral genera: the lentiviruses, betaretroviruses and alpharetroviruses. Comparison of the three structures reveals the features of the supramolecular organization of Gag that are conserved between genera and therefore reflect general principles of Gag-Gag interactions and the features that are specific to certain genera. All three Gag proteins assemble to form approximately spherical hexameric lattices with irregular defects. In all three genera, the N-terminal domain of CA is arranged in hexameric rings around large holes. Where the rings meet, 2-fold densities, assigned to the C-terminal domain of CA, extend between adjacent rings, and link together at the 6-fold symmetry axis with a density, which extends toward the center of the particle into the nucleic acid layer. Although this general arrangement is conserved, differences can be seen throughout the CA and spacer peptide regions. These differences can be related to sequence differences among the genera. We conclude that the arrangement of the structural domains of CA is well conserved across genera, whereas the relationship between CA, the spacer peptide region, and the nucleic acid is more specific to each genus.