The intrinsically disordered C-terminal domain of the measles virus nucleoprotein interacts with the C-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded.
The intrinsically disordered C-terminal domain of the measles virus nucleoprotein interacts with the C-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded.
复制标题
DOI：
10.1110/ps.051411805
复制
发表时间：
2005-08
期刊：
影响因子：
8
通讯作者：
Longhi, Sonia
中科院分区：
文献类型：
--
作者：
Bourhis, Jean-Marie;Receveur-Brechot, Veronique;Oglesbee, Michael;Zhang, Xinsheng;Buccellato, Matthew;Darbon, Herve;Canard, Bruno;Finet, Stephanie;Longhi, Sonia
麻疹病毒是单链病毒目中的一种负义单链 RNA 病毒，该病毒目包括多种人类病原体，包括狂犬病病毒、埃博拉病毒、尼帕病毒和亨德拉病毒。麻疹病毒核蛋白由结构化的 N 端结构域和本质上无序的 C 端结构域 NTAIL（氨基酸 401-525）组成，NTAIL 在病毒磷蛋白的 C 端结构域（XD，氨基酸 459-507）存在的情况下经历诱导折叠。在 NTAIL 中，鉴定出参与与 P 结合和诱导折叠的 α-螺旋分子识别元件（α-MoRE，aa 488-499），然后在 XD 的晶体结构中进行观察。利用小角X射线散射，我们推导出了XD和NTAIL之间复合物的低分辨率结构模型，这表明尽管P诱导α-MoRE内折叠，但大多数NTAIL在复合物中仍然是无序的。该模型由一个扩展形状组成，该形状可容纳 NTAIL 无序 N 末端区域采用的多种构象，以及一个庞大的球状区域，对应于 XD 和 NTAIL 的 C 末端 (aa 486-525)。利用表面等离振子共振、圆二色性、荧光光谱和异核磁共振，我们证明 NTAIL 有一个额外的位点 (aa 517-525) 参与与 XD 的结合，但不参与非结构到结构的转变。这项工作提供了证据，表明本质上无序的结构域可以与它们的伙伴建立复杂的相互作用，并且可以通过多个位点联系它们，而这些位点不一定都获得规则的二级结构。
Measles virus is a negative-sense, single-stranded RNA virus within theMononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses. Themeasles virus nucleoprotein consists of a structured N-terminal domain, and of an intrinsically disordered C-terminal domain, NTAIL (aa 401–525), which undergoes induced folding in the presence of the C-terminal domain (XD, aa 459–507) of the viral phosphoprotein. With in NTAIL, an α-helical molecular recognition element (α-MoRE, aa 488–499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD. Using small-angle X-ray scattering, we have derived a low-resolution structural model of the complex between XD and NTAIL, which shows that most of NTAIL remains disordered in the complex despite P-induced folding within the α-MoRE. The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N-terminal region of NTAIL, and of a bulky globular region, corresponding to XD and to the C terminus of NTAIL (aa 486–525). Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that NTAIL has an additional site (aa 517–525) involved in binding to XD but not in the unstructured-to-structured transition. This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure.