title: Nucleocapsid protein of SARS coronavirus tightly binds to human cyclophilin A.
abstract: 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 160nM. 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.
authors.affiliation: Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Haibin
authors.initials: H
authors.lastname: Luo
authors.forename: Suxin
authors.initials: S
authors.lastname: Zheng
authors.forename: Chunshan
authors.initials: C
authors.lastname: Gui
authors.forename: Liduo
authors.initials: L
authors.lastname: Yue
authors.forename: Changying
authors.initials: C
authors.lastname: Yu
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Peilan
authors.initials: P
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shen
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Luo
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Donglu
authors.initials: D
authors.lastname: Bai
authors.forename: Jingkang
authors.initials: J
authors.lastname: Shen
authors.forename: Yiming
authors.initials: Y
authors.lastname: Yang
authors.forename: Fangqiu
authors.initials: F
authors.lastname: Li
authors.forename: Jianping
authors.initials: J
authors.lastname: Zuo
authors.forename: Rolf
authors.initials: R
authors.lastname: Hilgenfeld
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology; D000086462:Coronavirus Nucleocapsid Proteins; D021984:Cyclophilin A / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D045169:Severe Acute Respiratory Syndrome; D020349:Surface Plasmon Resonance
chemical_list: D000086462:Coronavirus Nucleocapsid Proteins; D019590:Nucleocapsid Proteins; D021984:Cyclophilin A