Johansson Kenth, Bourhis Jean-Marie, Campanacci Valerie, Cambillau Christian, Canard Bruno, Longhi Sonia
Architecture et Fonction des Macromolécules Biologiques, UMR 6098 CNRS et Université Aix-Marseille, 13288 Marseille 09, France.
J Biol Chem. 2003 Nov 7;278(45):44567-73. doi: 10.1074/jbc.M308745200. Epub 2003 Aug 27.
Measles virus is a negative-sense, single-stranded RNA virus belonging to the Mononegavirales order which comprises several human pathogens such as Ebola, Nipah, and Hendra viruses. The phosphoprotein of measles virus is a modular protein consisting of an intrinsically disordered N-terminal domain (Karlin, D., Longhi, S., Receveur, V., and Canard, B. (2002) Virology 296, 251-262) and of a C-terminal moiety (PCT) composed of alternating disordered and globular regions. We report the crystal structure of the extreme C-terminal domain (XD) of measles virus phosphoprotein (aa 459-507) at 1.8 A resolution. We have previously reported that the C-terminal domain of measles virus nucleoprotein, NTAIL, is intrinsically unstructured and undergoes induced folding in the presence of PCT (Longhi, S., Receveur-Brechot, V., Karlin, D., Johansson, K., Darbon, H., Bhella, D., Yeo, R., Finet, S., and Canard, B. (2003) J. Biol. Chem. 278, 18638-18648). Using far-UV circular dichroism, we show that within PCT, XD is the region responsible for the induced folding of NTAIL. The crystal structure of XD consists of three helices, arranged in an anti-parallel triple-helix bundle. The surface of XD formed between helices alpha2 and alpha3 displays a long hydrophobic cleft that might provide a complementary hydrophobic surface to embed and promote folding of the predicted alpha-helix of NTAIL. We present a tentative model of the interaction between XD and NTAIL. These results, beyond presenting the first measles virus protein structure, shed light both on the function of the phosphoprotein at the molecular level and on the process of induced folding.
麻疹病毒是一种负链单链RNA病毒，属于单股负链RNA病毒目，该目包含几种人类病原体，如埃博拉病毒、尼帕病毒和亨德拉病毒。麻疹病毒的磷蛋白是一种模块化蛋白，由一个内在无序的N端结构域（卡林，D.，隆吉，S.，勒塞弗尔，V.，和卡纳德，B.（2002年）《病毒学》296，251 - 262）和一个由交替的无序和球状区域组成的C端部分（PCT）组成。我们报告了麻疹病毒磷蛋白极端C端结构域（XD，氨基酸459 - 507）在1.8埃分辨率下的晶体结构。我们之前曾报道，麻疹病毒核蛋白的C端结构域NTAIL本质上是无结构的，并且在PCT存在的情况下会发生诱导折叠（隆吉，S.，勒塞弗尔 - 布雷肖，V.，卡林，D.，约翰松，K.，达尔邦，H.，贝拉，D.；杨，R.，菲内，S.，和卡纳德，B.（2003年）《生物化学杂志》278，18638 - 18648）。使用远紫外圆二色性，我们表明在PCT内，XD是负责NTAIL诱导折叠的区域。XD的晶体结构由三个螺旋组成，排列成一个反平行的三螺旋束。在螺旋α2和α3之间形成的XD表面显示出一个长的疏水裂缝，这可能提供一个互补的疏水表面来嵌入并促进NTAIL预测的α螺旋的折叠。我们提出了XD与NTAIL相互作用的初步模型。这些结果，除了展示第一个麻疹病毒蛋白结构外，还在分子水平上揭示了磷蛋白的功能以及诱导折叠的过程。
