Asenjo Ana, Mendieta Jesús, Gómez-Puertas Paulino, Villanueva Nieves
Instituto de Salud Carlos III, Ctra. Majadahonda, Madrid 28220, Spain.
Virus Res. 2008 Mar;132(1-2):160-73. doi: 10.1016/j.virusres.2007.11.013. Epub 2008 Jan 7.
Human respiratory syncytial virus (HRSV) P protein, 241 amino acid long, is a structural homotetrameric phosphoprotein. Viral transcription and replication processes are dependent on functional P protein interactions inside viral ribonucleoprotein complexes (RNPs). Binding capacity to RNPs proteins and transcription and replication complementation analyses, using inactive P protein variants, have identified residues essential for functional interactions with itself, L, N and M2-1 proteins. P protein may establish some of these interactions as monomer, but efficient viral transcription and replication requires P protein oligomerization through the central region of the molecule. A structurally stable three-dimensional model has been generated in silico for this region (residues 98-158). Our analysis has indicated that P protein residues L135, D139, E140 and L142 are involved in homotetramerization. Additionally, the residues D136, S156, T160 and E179 appear to be essential for P protein activity on viral RNA synthesis and very high turnover phosphorylation at S143, T160 and T210 could regulate it. Thus, compounds targeted to those of these residues, located in the modeled three-dimensional structure, could have specific anti-HRSV effect.
人呼吸道合胞病毒（HRSV）的P蛋白由241个氨基酸组成，是一种结构性同四聚体磷蛋白。病毒转录和复制过程依赖于病毒核糖核蛋白复合物（RNP）内功能性P蛋白的相互作用。使用无活性P蛋白变体进行的与RNP蛋白的结合能力以及转录和复制互补分析，已确定了与自身、L、N和M2-1蛋白进行功能性相互作用所必需的残基。P蛋白可能以单体形式建立其中一些相互作用，但有效的病毒转录和复制需要P蛋白通过分子的中心区域进行寡聚化。已在计算机上为该区域（残基98-158）生成了一个结构稳定的三维模型。我们的分析表明，P蛋白残基L135、D139、E140和L142参与同四聚化。此外，残基D136、S156、T160和E179似乎对P蛋白在病毒RNA合成上的活性至关重要，并且S143、T160和T210处的非常高的周转磷酸化可能对其进行调节。因此，针对位于模拟三维结构中的这些残基的化合物可能具有特异性抗HRSV作用。
