Structure and self-association of the Rous sarcoma virus capsid protein
Structure and self-association of the Rous sarcoma virus capsid protein
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DOI：
10.1016/s0969-2126(00)00148-9
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发表时间：
2000-06-15
期刊：
影响因子：
5.7
通讯作者：
Rossmann, MG
中科院分区：
文献类型：
--
作者：
Kingston, RL;Fitzon-Ostendorp, T;Rossmann, MG
背景：逆转录病毒（如劳斯肉瘤病毒（RSV））的衣壳蛋白（CA）由两个独立折叠的结构域组成。CA的功能作为一个多蛋白的一部分，在颗粒组装和出芽，此外，形成一个外壳的基因组RNA在成熟的，传染性virus.Results：RSV CA的N-和C-末端结构域的结构已确定由X-射线晶体学和溶液核磁共振（NMR）光谱，分别。N-末端结构域在N末端包含七个α螺旋和一个短发夹。N-末端结构域通过晶体内的小的、紧密堆积的、双重对称的界面相关联，不同于先前对其他逆转录病毒CA所描述的那些。C-末端结构域是四个α螺旋的紧凑束，尽管最后几个残基是无序的。在稀溶液中，RSV CA主要是单体。然而，我们发现，使用电子显微镜，完整的RSV CA可以组装在体外形成管状结构的环形寡聚体和平面单层。这两种模式的组装发生在类似的解决方案的条件下，片材和管表现出长程order.Conclusions：CA的三级结构是保守的主要逆转录病毒属，但序列的变化足以引起关联行为的变化。CA形成所有成熟逆转录病毒中病毒核心的外壳。然而，病毒的核心形态不同。与此观察结果一致，我们发现RSV和人类免疫缺陷病毒1型的衣壳蛋白在稀溶液中表现出不同的缔合行为，并在体外组装成不同的结构。
Background: The capsid protein (CA) of retroviruses; such as Rous sarcoma virus (RSV), consists of two independently folded domains. CA functions as part of a polyprotein during particle assembly and budding and, in addition, forms a shell encapsidating the genomic RNA in the mature, infectious virus.Results: The structures of the N- and C-terminal domains of RSV CA have been determined by X-ray crystallography and solution nuclear magnetic resonance (NMR) spectroscopy, respectively. The N-terminal domain comprises seven a helices and a short beta hairpin at the N terminus. The N-terminal domain associates through a small, tightly packed, twofold symmetric interface within the crystal, different from those previously described for other retroviral CAs. The C-terminal domain is a compact bundle of four alpha helices, although the last few residues are disordered. In dilute solution, RSV CA is predominantly monomeric. We show, however, using electron microscopy, that intact RSV CA can assemble in vitro to form both tubular structures constructed from toroidal oligomers and planar monolayers. Both modes of assembly occur under similar solution conditions, and both sheets and tubes exhibit long-range order.Conclusions: The tertiary structure of CA is conserved across the major retroviral genera, yet sequence variations are sufficient to cause change in associative behavior. CA forms the exterior shell of the viral core in all mature retroviruses. However, the core morphology differs between viruses. Consistent with this observation, we find that the capsid proteins of RSV and human immunodeficiency virus type 1 exhibit different associative behavior in dilute solution and assemble in vitro into different structures.