Deng Yiqun, Liu Jie, Zheng Qi, Yong Wei, Lu Min
Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA.
Structure. 2006 May;14(5):889-99. doi: 10.1016/j.str.2006.03.007.
Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct alpha-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.
严重急性呼吸综合征冠状病毒进入其靶细胞需要病毒刺突（S）糖蛋白进行大规模结构转变，以诱导病毒与细胞膜融合。在此，我们描述了从S2融合亚基高度保守的七肽重复（HR）区域衍生出的四个不同α螺旋结构域的鉴定及晶体结构。这四个结构域分别是一个反平行四链卷曲螺旋、一个平行三聚体卷曲螺旋、一个四螺旋束以及一个六螺旋束，后者可能是该蛋白最终的融合活性形式。综合来看，这四个结构域的结构和热力学特征提示了一种可能的机制，即最初被封闭在天然S糖蛋白刺突中的HR区域被释放并依次重新折叠，以促进膜融合。我们的结果为理解膜融合的调控提供了一个结构框架，并应能指导干预严重急性呼吸综合征冠状病毒进入过程的研究工作。
