关于SARS-CoV-2演变的结构和功能见解 KP.3.1.1 尖端蛋白质
Ziqi Feng1, Jiachen Huang1, Sabyasachi Baboo2
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Cell reports
|July 6, 2025
概括
KP.3.1.1 SARS-CoV-2 变种有一个新的甘氨酸位,不影响 hACE2 结合,但突变会影响抗体逃逸. 这揭示了对病毒进化和免疫逃避策略的洞察力.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- SARS-CoV-2 JN.1-亚系KP.3.1.1是全球占主导地位的变种.
- 这种变种表现出增加的传染性和抗体逃逸特性.
研究的目的:
- 调查KP.3.1.1尖端蛋白中突变和缺失对HACE2结合和抗体逃逸的影响.
- 了解KP.3.1.1突变的结构和功能后果.
主要方法:
- 质谱测量以识别糖甘位点变化.
- 低温电子显微镜 (cryo-EM) 用于确定结构变化.
- 对尖端蛋白-hACE2相互作用的分析.
主要成果:
- 证实了新的N30甘氨酸位点,改变了邻近的甘氨酸形式,但没有显著影响尖峰结构或 hACE2结合.
- 低温EM结构显示,尖峰形状或受体结合域方向没有重大变化.
- 在HACE2结合方面,F456L和Q493E突变之间的表观效应得到证实.
结论:
- 包括N30甘氨酸和Q493E在内的KP.3.1.1突变不会显著阻碍HACE2结合.
- 2023年后的SARS-CoV-2进化涉及将其他sarbecoviruses中发现的回归纳入其中.
- 这些发现提供了对病毒演变,免疫逃避以及SARS-CoV-2变种感染性的结构基础的见解.
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