Nucleocapsid protein of SARS coronavirus tightly binds to human cyclophilin A

Biochem Biophys Res Commun. 2004 Aug 27;321(3):557-65. doi: 10.1016/j.bbrc.2004.07.003.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Computational Biology
  • Coronavirus Nucleocapsid Proteins
  • Cyclophilin A / genetics
  • Cyclophilin A / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nucleocapsid Proteins / genetics
  • Nucleocapsid Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Reproducibility of Results
  • Sequence Alignment
  • Severe Acute Respiratory Syndrome
  • Severe acute respiratory syndrome-related coronavirus / genetics
  • Severe acute respiratory syndrome-related coronavirus / metabolism*
  • Surface Plasmon Resonance


  • Coronavirus Nucleocapsid Proteins
  • Nucleocapsid Proteins
  • Cyclophilin A