Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, OX3 7BN Oxford, United Kingdom.
Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, OX3 7BN Oxford, United Kingdom
Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21514-21520. doi: 10.1073/pnas.1906717116. Epub 2019 Oct 7.
The bat-borne paramyxovirus, Sosuga virus (SosV), is one of many paramyxoviruses recently identified and classified within the newly established genus , family The envelope surface of SosV presents a receptor-binding protein (RBP), SosV-RBP, which facilitates host-cell attachment and entry. Unlike closely related hemagglutinin neuraminidase RBPs from other genera of the , SosV-RBP and other pararubulavirus RBPs lack many of the stringently conserved residues required for sialic acid recognition and hydrolysis. We determined the crystal structure of the globular head region of SosV-RBP, revealing that while the glycoprotein presents a classical paramyxoviral six-bladed β-propeller fold and structurally classifies in close proximity to paramyxoviral RBPs with hemagglutinin-neuraminidase (HN) functionality, it presents a receptor-binding face incongruent with sialic acid recognition. Hemadsorption and neuraminidase activity analysis confirms the limited capacity of SosV-RBP to interact with sialic acid in vitro and indicates that SosV-RBP undergoes a nonclassical route of host-cell entry. The close overall structural conservation of SosV-RBP with other classical HN RBPs supports a model by which pararubulaviruses only recently diverged from sialic acid binding functionality.
携带蝙蝠的副粘病毒，索苏加病毒（SosV），是最近在新成立的属、科中鉴定和分类的许多副粘病毒之一。SosV 的包膜表面呈现一种受体结合蛋白（RBP），即 SosV-RBP，它促进了宿主细胞的附着和进入。与来自其他属的密切相关的血凝素神经氨酸酶 RBPs 不同，SosV-RBP 和其他副 rubulavirus RBPs 缺乏许多严格保守的残基，这些残基对于识别和水解唾液酸是必需的。我们确定了 SosV-RBP 球状头部区域的晶体结构，揭示了虽然糖蛋白呈现出经典的副粘病毒六叶β-三叶桨折叠结构，并且在结构上与具有血凝素神经氨酸酶（HN）功能的副粘病毒 RBPs 密切分类，但它呈现出与唾液酸识别不一致的受体结合面。血吸附和神经氨酸酶活性分析证实了 SosV-RBP 在体外与唾液酸相互作用的能力有限，并表明 SosV-RBP 经历了一种非经典的宿主细胞进入途径。SosV-RBP 与其他经典 HN RBPs 的整体结构高度保守，支持了一种模型，即副 rubulaviruses 最近才从唾液酸结合功能上分化出来。
