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1. chinaXiv:202003.00046 [pdf]

Cryo-EM structure of SARS-CoV spike glycoprotein in post-fusion state

Fan, Xiaoyi; Cao, Duanfang; Kong, Lingfei; Zhang, Xinzheng
Subjects: Biology >> Virology

冠状病毒SARS-CoV,MERS-CoV和新发现的2019-nCoV所引发的传染性疾病严重威胁着人类的生命健康安全。位于冠状病毒表面的spike(S)糖蛋白在病毒传播及感染过程中负责结合宿主细胞受体,融合细胞中的膜结构等关键步骤,是病毒重要的药物靶点。其中在冠状病毒中高度保守的S2亚基作为融膜机器,介导了病毒与宿主之间的膜融合过程。我们运用冷冻电镜单颗粒三维重构技术解析了SARS-CoV S糖蛋白的融膜后构象的结构,展示了S2亚基在融膜过程中的结构特点和构象变化。结合保守性比对和糖基化修饰指认,这项工作分析了位于S2亚基的潜在药物靶点,有益于相关疫苗和药物的开发和设计。

submitted time 2020-03-06 Hits16166Downloads3161 Comment 0

2. chinaXiv:201605.01484 [pdf]

Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization

Zhang, Liman; Ruan, Jianbin; Tong, Alexander B.; Yin, Qian; Li, Yang; David, Liron; Lu, Alvin; Wu, Hao; Zhang, Liman; Ruan, Jianbin; Tong, Alexander B.; Yin, Qian; Li, Yang; David, Liron; Lu, Alvin; Wu, Hao; Chen, Shuobing; Wu, Jiayi; Ouyang, Qi; Mao, Youdong
Subjects: Biology >> Biophysics

The NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, such as the bacterial rod protein PrgJ, and recruit NLR family CARD-containing protein 4 (NLRC4) as the inflammasome adapter to activate innate immunity. We found that the PrgJ-NAIP2-NLRC4 inflammasome is assembled into multisubunit disk-like structures through a unidirectional adenosine triphosphatase polymerization, primed with a single PrgJ-activated NAIP2 per disk. Cryo-electron microscopy (cryo-EM) reconstruction at subnanometer resolution revealed a similar to 90 degrees hinge rotation accompanying NLRC4 activation. Unlike in the related heptameric Apaf-1 apoptosome, in which each subunit needs to be conformationally activated by its ligand before assembly, a single PrgJ-activated NAIP2 initiates NLRC4 polymerization in a domino-like reaction to promote the disk assembly. These insights reveal the mechanism of signal amplification in NAIP-NLRC4 inflammasomes.

submitted time 2016-05-12 Hits1601Downloads918 Comment 0

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