Structural characteristics of Heparan sulfate required for the binding with the virus processing Enzyme Furin.
Structural characteristics of Heparan sulfate required for the binding with the virus processing Enzyme Furin.
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DOI：
10.1007/s10719-021-10018-8
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发表时间：
2022-06
影响因子：
3
通讯作者：
Qiu H
中科院分区：
文献类型：
--
作者：
Zeng J;Meng Y;Chen SY;Zhao G;Wang L;Zhang EX;Qiu H
Furin是蛋白转化酶家族九成员之一。Furin可切割含有多碱基残基的蛋白质，其中包括许多病毒糖蛋白，如SARS-Cov-2刺突蛋白。裂解是激活蛋白质所必需的。目前，调节Furin活性的机制在很大程度上仍然未知。本研究通过生化和基因分析证明Furin是一种新型肝素/硫酸肝素结合蛋白。基于生物层干涉测定的KD为9.78 nM。此外，我们发现磺化程度、位点特异性磺化（n -磺化和3- o -磺化）和伊杜醛酸是结合的主要结构决定因素。此外，我们发现当肝素与Furin或Furin底物预混合时，肝素抑制Furin的酶活性。我们还发现Furin与不同来源的细胞结合，其中与肺来源细胞的结合最强。这些数据可以促进我们对Furin的工作机制的理解，并将有利于基于Furin的药物发现，如靶向硫酸肝素和Furin相互作用的抑制剂，以抑制病毒感染。在线版本包含补充资料，下载地址：10.1007/s10719-021-10018-8。
Furin is one of the nine-member proprotein convertase family. Furin cleaves proteins with polybasic residues, which includes many viral glycoproteins such as SARS-Cov-2 spike protein. The cleavage is required for the activation of the proteins. Currently, the mechanisms that regulate Furin activity remain largely unknown. Here we demonstrated that Furin is a novel heparin/heparan sulfate binding protein by the use of biochemical and genetic assays. The KD is 9.78 nM based on the biolayer interferometry assay. Moreover, we found that sulfation degree, site-specific sulfation (N-sulfation and 3-O-sulfation), and iduronic acid are the major structural determinants for the binding. Furthermore, we found that heparin inhibits the enzymatic activity of Furin when pre-mixes heparin with either Furin or Furin substrate. We also found that the Furin binds with cells of different origin and the binding with the cells of lung origin is the strongest one. These data could advance our understanding of the working mechanism of Furin and will benefit the Furin based drug discovery such as inhibitors targeting the interaction between heparan sulfate and Furin for inhibition of viral infection. The online version contains supplementary material available at 10.1007/s10719-021-10018-8.
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SARS-COV-2峰值的氟蛋白切割会促进，但对于感染和细胞融合并不是必不可少的。
影响因子：
6.7
作者：
Papa G;Mallery DL;Albecka A;Welch LG;Cattin-Ortolá J;Luptak J;Paul D;McMahon HT;Goodfellow IG;Carter A;Munro S;James LC
通讯作者：
James LC
影响因子：
6.7
作者：
Mycroft-West, Courtney J.;Su, Dunhao;Skidmore, Mark A.
通讯作者：
Skidmore, Mark A.
DOI：
10.1073/pnas.95.10.5762
发表时间：
1998-05-12
影响因子：
11.1
作者：
Volchkov, VE;Feldmann, H;Klenk, HD
通讯作者：
Klenk, HD
影响因子：
3.1
作者：
Lee, Mee Jeong
通讯作者：
Lee, Mee Jeong
影响因子：
7.6
作者：
Kim, So Young;Jin, Weihua;Linhardt, Robert J.
通讯作者：
Linhardt, Robert J.