Structural characteristics of Heparan sulfate required for the binding with the virus processing Enzyme Furin
| Autor: | Hong Qiu, Jiaxin Zeng, Lianchun Wang, Yuan Meng, Gaofeng Zhao, En-Xin Zhang, Shi-Yi Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
animal structures
viruses Virus infection Iduronic acid Heparan sulfate Biochemistry chemistry.chemical_compound Sulfation medicine Humans Molecular Biology Furin chemistry.chemical_classification biology Chemistry Heparin SARS-CoV-2 Cell Biology Carbohydrate-protein interaction Proprotein convertase Cell biology embryonic structures Spike Glycoprotein Coronavirus biology.protein Heparan sulfate binding Original Article Heparitin Sulfate Glycoprotein medicine.drug |
| Zdroj: | Glycoconjugate Journal |
| ISSN: | 1573-4986 0282-0080 |
| Popis: | 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. Supplementary information The online version contains supplementary material available at 10.1007/s10719-021-10018-8. |
| Databáze: | OpenAIRE |
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