Department of Zoology, University of Oxford, Oxford, United Kingdom.
PLoS One. 2012;7(3):e31719. doi: 10.1371/journal.pone.0031719. Epub 2012 Mar 5.
Paramyxovirinae are a large group of viruses that includes measles virus and parainfluenza viruses. The viral Phosphoprotein (P) plays a central role in viral replication. It is composed of a highly variable, disordered N-terminus and a conserved C-terminus. A second viral protein alternatively expressed, the V protein, also contains the N-terminus of P, fused to a zinc finger. We suspected that, despite their high variability, the N-termini of P/V might all be homologous; however, using standard approaches, we could previously identify sequence conservation only in some Paramyxovirinae. We now compared the N-termini using sensitive sequence similarity search programs, able to detect residual similarities unnoticeable by conventional approaches. We discovered that all Paramyxovirinae share a short sequence motif in their first 40 amino acids, which we called soyuz1. Despite its short length (11-16aa), several arguments allow us to conclude that soyuz1 probably evolved by homologous descent, unlike linear motifs. Conservation across such evolutionary distances suggests that soyuz1 plays a crucial role and experimental data suggest that it binds the viral nucleoprotein to prevent its illegitimate self-assembly. In some Paramyxovirinae, the N-terminus of P/V contains a second motif, soyuz2, which might play a role in blocking interferon signaling. Finally, we discovered that the P of related Mononegavirales contain similarly overlooked motifs in their N-termini, and that their C-termini share a previously unnoticed structural similarity suggesting a common origin. Our results suggest several testable hypotheses regarding the replication of Mononegavirales and suggest that disordered regions with little overall sequence similarity, common in viral and eukaryotic proteins, might contain currently overlooked motifs (intermediate in length between linear motifs and disordered domains) that could be detected simply by comparing orthologous proteins.
副黏病毒科是一大类病毒，包括麻疹病毒和副流感病毒。病毒的磷蛋白（P）在病毒复制中起着核心作用。它由一个高度可变的、无规的 N 端和一个保守的 C 端组成。第二个交替表达的病毒蛋白，V 蛋白，也包含 P 的 N 端，融合到一个锌指上。我们怀疑，尽管它们的变异性很高，但 P/V 的 N 端可能都是同源的；然而，使用标准方法，我们以前只能在一些副黏病毒科中识别出序列保守性。我们现在使用敏感的序列相似性搜索程序来比较 N 端，这些程序能够检测到常规方法无法察觉的残留相似性。我们发现所有副黏病毒科在它们的前 40 个氨基酸中都有一个短的序列基序，我们称之为 soyuz1。尽管它的长度很短（11-16aa），但有几个论据让我们得出结论，soyuz1 可能是通过同源进化而来的，而不是线性基序。在如此长的进化距离上的保守性表明 soyuz1 发挥了关键作用，实验数据表明它结合了病毒核蛋白，以防止其非法自组装。在一些副黏病毒科中，P/V 的 N 端包含第二个基序 soyuz2，它可能在阻断干扰素信号方面发挥作用。最后，我们发现相关的 Mononegavirales 的 P 蛋白在其 N 端含有类似的被忽视的基序，并且它们的 C 端具有以前未被注意到的结构相似性，表明它们有共同的起源。我们的结果提出了一些关于 Mononegavirales 复制的可测试假说，并表明在病毒和真核蛋白中常见的具有很少整体序列相似性的无序区域可能包含目前被忽视的基序（长度介于线性基序和无序结构域之间），通过比较直系同源蛋白就可以检测到这些基序。
