在膜融合pH下,流感血凝素的结构转变
Donald J Benton1, Steven J Gamblin2, Peter B Rosenthal3
1Structural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK. donald.benton@crick.ac.uk.
Nature
|May 29, 2020
概括
流感病毒使用它的血凝素 (HA) 糖蛋白与宿主细胞膜融合. 这项研究揭示了新的HA结构,包括三螺旋线圈,对于理解病毒进入和膜融合机制至关重要.
科学领域:
- 结构生物学
- 病毒学
- 生物化学
背景情况:
- 封装病毒,如流感病毒,通过将其脂质封装与细胞膜融合来感染细胞.
- 病毒包膜糖蛋白调解这种融合过程,与细胞受体结合并促进膜融合.
- 对于流感,血凝素 (HA) 是关键的糖蛋白,在细胞吸收后与内体膜进行融合.
研究的目的:
- 在低pH诱导的膜融合过程中研究流感血凝素 (HA) 的动态结构变化.
- 确定和描述以前未被描述的化过程中涉及的HA的中间结构.
主要方法:
- 使用单粒子冷电子显微镜直接绘制HA结构变化的图像.
- 在pH值为5.0的不同时间内化HA,以捕捉形状重组的不同阶段.
主要成果:
- 发现了三种不同,以前未被描述的HA形式.
- 一个值得注意的发现是由HA2子单元形成的150 Å长的三螺旋结构.
- 这些结构表明HA2可能是病毒和内体膜的桥梁机制.
结论:
- 已识别的HA结构为推动病毒膜融合的形状重组提供了新的见解.
- 三重螺旋HA2线圈可能在病毒和宿主细胞膜之间的融合事件中发挥关键作用.
- 这项研究有助于更好地了解流感病毒的入侵,并为抗病毒疗法提供了潜在的目标.
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