Zhu Jieqing, Zhang Catherine W-H, Qi Yipeng, Tien Po, Gao George F
Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Zhongguancun Beiyitiao, Beijing 100080, China.
Biochem Biophys Res Commun. 2002 Dec 20;299(5):897-902. doi: 10.1016/s0006-291x(02)02761-4.
Recent studies have shown that paramyxovirus might adopt a similar molecular mechanism of virus entry and fusion in which the attachment glycoprotein binds receptor/s and triggers the conformational changes of the fusion protein. There are two conserved regions of heptad repeat (HR1 and HR2) in the fusion protein and they were shown with fusion-inhibition effects in many paramyxoviruses, including measles virus. They also appear to show characteristic structure in the fusion core: the HR1/HR2 forms stable six-helix coiled-coil centered by HR1 and is surrounded by HR2 (trimer of HR1/HR2), which represents the post-fusion conformational structure. In this study, we expressed the HR1 and HR2 of measles virus fusion protein as a single chain (named 2-Helix) and subsequently tested its formation of trimer. Indeed, the results do show that the HR1 and HR2 interact with each other and form stable six-helix coiled-coil bundle. This is the first member in genus Morbillivirus of family Paramyxoviridae to be confirmed with this characteristic structure and provides the basis for the HR2-inhibition effects on virus fusion/entry for measles virus.
最近的研究表明，副粘病毒可能采用类似的病毒进入和融合分子机制，即附着糖蛋白结合受体并触发融合蛋白的构象变化。融合蛋白中有两个七肽重复序列的保守区域（HR1和HR2），在包括麻疹病毒在内的许多副粘病毒中它们都表现出融合抑制作用。它们在融合核心似乎也呈现出特征性结构：HR1/HR2形成以HR1为中心的稳定六螺旋卷曲螺旋，并被HR2包围（HR1/HR2三聚体），这代表融合后构象结构。在本研究中，我们将麻疹病毒融合蛋白的HR1和HR2表达为单链（命名为2-Helix），随后测试其三聚体的形成。事实上，结果确实表明HR1和HR2相互作用并形成稳定的六螺旋卷曲螺旋束。这是副粘病毒科麻疹病毒属中首个被证实具有这种特征结构的成员，并为HR2对麻疹病毒融合/进入的抑制作用提供了基础。
