ICCAS OpenIR
Maturation Mechanism of Severe Acute Respiratory Syndrome (SARS) Coronavirus 3C-like Proteinase
Li, Chunmei2; Qi, Yifei2; Teng, Xin; Yang, Zongchang; Wei, Ping2; Zhang, Changsheng2; Tan, Lei; Zhou, Lu; Liu, Ying1; Lai, Luhua1,2
2010-09-03
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
ISSN0021-9258
Volume285Issue:36Pages:28134-28140
AbstractThe 3C-like proteinase (3CL(pro)) of the severe acute respiratory syndrome (SARS) coronavirus plays a vital role in virus maturation and is proposed to be a key target for drug design against SARS. Various in vitro studies revealed that only the dimer of the matured 3CL(pro) is active. However, as the internally encoded 3CL(pro) gets matured from the replicase polyprotein by autolytic cleavage at both the N-terminal and the C-terminal flanking sites, it is unclear whether the polyprotein also needs to dimerize first for its auto-cleavage reaction. We constructed a large protein containing the cyan fluorescent protein (C), the N-terminal flanking substrate peptide of SARS 3CL(pro) (XX), SARS 3CL(pro) (3CLP), and the yellow fluorescent protein (Y) to study the autoprocessing of 3CL(pro) using fluorescence resonance energy transfer. In contrast to the matured 3CL(pro), the polyprotein, as well as the one-step digested product, 3CLP-Y-His, were shown to be monomeric in gel filtration and analytic ultracentrifuge analysis. However, dimers can still be induced and detected when incubating these large proteins with a substrate analog compound in both chemical cross-linking experiments and analytic ultracentrifuge analysis. We also measured enzyme activity under different enzyme concentrations and found a clear tendency of substrate-induced dimer formation. Based on these discoveries, we conclude that substrate-induced dimerization is essential for the activity of SARS-3CL(pro) in the polyprotein, and a modified model for the 3CL(pro) maturation process was proposed. As many viral proteases undergo a similar maturation process, this model might be generally applicable.
DOI10.1074/jbc.M109.095851
Indexed BySCI
Language英语
WOS IDWOS:000281404100056
PublisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation statistics
Cited Times:14[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.iccas.ac.cn/handle/121111/69958
Collection中国科学院化学研究所
Corresponding AuthorLai, Luhua
Affiliation1.Peking Univ, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, Beijing Natl Lab Mol Sci, Beijing 100871, Peoples R China
2.Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China
Recommended Citation
GB/T 7714
Li, Chunmei,Qi, Yifei,Teng, Xin,et al. Maturation Mechanism of Severe Acute Respiratory Syndrome (SARS) Coronavirus 3C-like Proteinase[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2010,285(36):28134-28140.
APA Li, Chunmei.,Qi, Yifei.,Teng, Xin.,Yang, Zongchang.,Wei, Ping.,...&Lai, Luhua.(2010).Maturation Mechanism of Severe Acute Respiratory Syndrome (SARS) Coronavirus 3C-like Proteinase.JOURNAL OF BIOLOGICAL CHEMISTRY,285(36),28134-28140.
MLA Li, Chunmei,et al."Maturation Mechanism of Severe Acute Respiratory Syndrome (SARS) Coronavirus 3C-like Proteinase".JOURNAL OF BIOLOGICAL CHEMISTRY 285.36(2010):28134-28140.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Li, Chunmei]'s Articles
[Qi, Yifei]'s Articles
[Teng, Xin]'s Articles
Baidu academic
Similar articles in Baidu academic
[Li, Chunmei]'s Articles
[Qi, Yifei]'s Articles
[Teng, Xin]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Li, Chunmei]'s Articles
[Qi, Yifei]'s Articles
[Teng, Xin]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.