Nucleocapsid protein of SARS coronavirus tightly binds to human cyclophilin A
| Autor: | Jianping Zuo, Xiaomin Luo, Hong Liu, Jianhua Shen, Haibin Luo, Yixue Li, Kaixian Chen, Changying Yu, Liduo Yue, Hualiang Jiang, Suxin Zheng, Jingkang Shen, Xu Shen, Tao Sun, Pei-Lan He, Fangqiu Li, Cheng Luo, Gang Pei, Yiming Yang, Chunshan Gui, Rolf Hilgenfeld, Jing Chen, Donglu Bai |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular SARS coronavirus Molecular Sequence Data Biophysics Sequence alignment Plasma protein binding Biology Severe Acute Respiratory Syndrome Biochemistry Article Protein–protein interaction Cyclophilin A Protein structure Coronavirus Nucleocapsid Proteins Humans Amino Acid Sequence Binding site Site-directed mutagenesis Molecular Biology Peptide sequence Nucleocapsid protein Binding Sites Computational Biology Reproducibility of Results Cell Biology Nucleocapsid Proteins Surface Plasmon Resonance Molecular biology Protein Structure Tertiary Severe acute respiratory syndrome-related coronavirus Mutagenesis Site-Directed Sequence Alignment Protein Binding |
| Zdroj: | Biochemical and Biophysical Research Communications |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2004.07.003 |
| Popis: | Severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for SARS infection. Nucleocapsid protein (NP) of SARS-CoV (SARS_NP) functions in enveloping the entire genomic RNA and interacts with viron structural proteins, thus playing important roles in the process of virus particle assembly and release. Protein–protein interaction analysis using bioinformatics tools indicated that SARS_NP may bind to human cyclophilin A (hCypA), and surface plasmon resonance (SPR) technology revealed this binding with the equilibrium dissociation constant ranging from 6 to 160 nM. The probable binding sites of these two proteins were detected by modeling the three-dimensional structure of the SARS_NP–hCypA complex, from which the important interaction residue pairs between the proteins were deduced. Mutagenesis experiments were carried out for validating the binding model, whose correctness was assessed by the observed effects on the binding affinities between the proteins. The reliability of the binding sites derived by the molecular modeling was confirmed by the fact that the computationally predicted values of the relative free energies of the binding for SARS_NP (or hCypA) mutants to the wild-type hCypA (or SARS_NP) are in good agreement with the data determined by SPR. Such presently observed SARS_NP–hCypA interaction model might provide a new hint for facilitating the understanding of another possible SARS-CoV infection pathway against human cell. |
| Databáze: | OpenAIRE |
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