Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein.
Crystal structure and solution state of the C-terminal head region of the narmovirus receptor binding protein.
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病毒监测的增加导致了许多未知的副粘病毒的分离和鉴定，迅速扩大了我们对副粘病毒多样性的理解，超出了已知属的范围。尽管存在这种多样性，但联合副粘病毒的一个关键特征是存在受体结合蛋白（RBP），其促进宿主细胞附着并在确定宿主范围方面发挥重要作用。在这里，我们研究的RBP提出的啮齿动物传播的副粘病毒莫斯曼和Nariva（MosV和NarV，分别），病毒，最近定义的Narmovirus属内的副粘病毒科的创始成员。二聚体MosV和NarV RBP的C-末端头部区域的晶体学分析表明，虽然这些糖蛋白保留了在其他副粘病毒RBP中发现的典型六叶β-螺旋桨折叠，但它们缺乏与已建立的副粘病毒宿主细胞受体进入途径相关的结构基序。与MosV-RBP和NarV-RBP经历与其他特征性副粘病毒不同的进入途径一致，基于结构的系统发育分析表明，这些六叶β-螺旋桨头部结构域形成了与其他副粘病毒RBP不同的单一结构类别。此外，使用集成的晶体学和小角X射线散射分析，我们确认MosV-RBP和NarV-RBP形成同型二聚体的安排，是不同于其他副粘病毒RBP所采用的。总而言之，这项调查提供了一个分子水平的蓝图，扩大了我们的理解，副粘病毒RBP的结构空间和功能多样性。遗传多样的副粘病毒在其受体结合蛋白（RBP）的呈递上是统一的，该受体结合蛋白与融合蛋白协同作用以促进宿主细胞进入。副粘病毒RBP的C-末端头部区域是宿主细胞嗜性和种间传播潜力的主要决定因素，形成依赖于蛋白质和聚糖受体特异性的结构上不同的类别。在这里，我们揭示了从Nariva病毒（NarV）和Mossman病毒（MosV），两个原型啮齿动物传播的副粘病毒在最近成立的属Narmovirus，家庭副粘病毒科的RBP的C-末端头部区域的架构。我们的分析表明，虽然narmoviruses保留了与副粘病毒RBP相关的一般结构特征，即六叶β螺旋桨折叠，但它们缺乏与已知受体介导的宿主细胞进入途径相关的结构基序。这项调查表明，RBP的narmoviruses表现出的病理生物学特征，是不同于其他副粘病毒。
Increased viral surveillance has led to the isolation and identification of numerous uncharacterized paramyxoviruses, rapidly expanding our understanding of paramyxoviral diversity beyond the bounds of known genera. Despite this diversity, a key feature that unites paramyxoviruses is the presence of a receptor-binding protein (RBP), which facilitates host-cell attachment and plays a fundamental role in determining host range. Here, we study the RBP presented on the surface of rodent-borne paramyxoviruses Mossman and Nariva (MosV and NarV, respectively), viruses that constitute founding members of the recently defined Narmovirus genus within the Paramyxoviridae family. Crystallographic analysis of the C-terminal head region of the dimeric MosV and NarV RBPs demonstrates that while these glycoproteins retain the canonical six-bladed β-propeller fold found in other paramyxoviral RBPs, they lack the structural motifs associated with established paramyxovirus host-cell receptor entry pathways. Consistent with MosV-RBP and NarV-RBP undergoing a distinct entry pathway from other characterized paramyxoviruses, structure-based phylogenetic analysis demonstrates that these six-bladed β-propeller head domains form a singular structural class that is distinct from other paramyxoviral RBPs. Additionally, using an integrated crystallographic and small-angle X-ray scattering analysis, we confirm that MosV-RBP and NarV-RBP form homodimeric arrangements that are distinct from those adopted by other paramyxovirus RBPs. Altogether, this investigation provides a molecular-level blueprint of the narmovirus RBP that broadens our understanding of the structural space and functional diversity available to paramyxovirus RBPs. Genetically diverse paramyxoviruses are united in their presentation of a receptor-binding protein (RBP), which works in concert with the fusion protein to facilitate host-cell entry. The C-terminal head region of the paramyxoviral RBP, a primary determinant of host-cell tropism and inter-species transmission potential, forms structurally distinct classes dependent upon protein and glycan receptor specificity. Here, we reveal the architecture of the C-terminal head region of the RBPs from Nariva virus (NarV) and Mossman virus (MosV), two archetypal rodent-borne paramyxoviruses within the recently established genus Narmovirus, family Paramyxoviridae. Our analysis reveals that while narmoviruses retain the general architectural features associated with paramyxoviral RBPs, namely, a six-bladed β-propeller fold, they lack the structural motifs associated with known receptor-mediated host-cell entry pathways. This investigation indicates that the RBPs of narmoviruses exhibit pathobiological features that are distinct from those of other paramyxoviruses.
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