1] Université Grenoble Alpes, Unit of Virus Host Cell Interactions, Grenoble, France. [2] CNRS, Unit of Virus Host Cell Interactions, Grenoble, France.
International Centre for Research in Infectiology (CIRI), INSERM U1111-CNRS UMR5308, Université Lyon 1, Ecole Normale Supérieure de Lyon, Lyon, France.
Nat Struct Mol Biol. 2014 Sep;21(9):754-9. doi: 10.1038/nsmb.2868. Epub 2014 Aug 10.
Nipah virus (NiV) is a highly pathogenic emergent paramyxovirus causing deadly encephalitis in humans. Its replication requires a constant supply of unassembled nucleoprotein (N(0)) in complex with its viral chaperone, the phosphoprotein (P). To elucidate the chaperone function of P, we reconstituted NiV the N(0)-P core complex and determined its crystal structure. The binding of the N-terminal region of P blocks the polymerization of N by interfering with subdomain exchange between N protomers and keeps N(0) in an open conformation, ready to grasp an RNA molecule. We found that a peptide derived from the N-binding region of P protects cells against viral infection and demonstrated by structure-based mutagenesis that this peptide acts by inhibiting N(0)-P formation. These results provide new insights about the assembly of N along genomic RNA and validate the N(0)-P complex as a target for drug development.
尼帕病毒（NiV）是一种高致病性的新兴副粘病毒，可导致人类致命性脑炎。其复制需要不断供应与病毒伴侣蛋白磷蛋白（P）结合的未组装核蛋白（N(0)）。为了阐明 P 的伴侣功能，我们重建了 NiV 的 N(0)-P 核心复合物，并确定了其晶体结构。P 的 N 端区域的结合通过干扰 N 原聚体之间的亚结构域交换来阻止 N 的聚合，并使 N(0)保持开放构象，准备抓住 RNA 分子。我们发现，源自 P 的 N 结合区的肽可保护细胞免受病毒感染，并通过基于结构的诱变证明，该肽通过抑制 N(0)-P 的形成起作用。这些结果提供了关于基因组 RNA 上 N 组装的新见解，并验证了 N(0)-P 复合物作为药物开发的靶标。
