Journal article

Identification of residues involved in NS2 homodimerization and elucidation of their impact on the HCV life cycle

AA Gorzin, PA Ramsland, G Tachedjian, EJ Gowans



The NS2 protein of hepatitis C virus (HCV) plays a critical role in virus morphogenesis and infectivity. The crystal structure of the C-terminus of the NS2 protein (NS2(Pro)) from the H77 strain indicates that NS2(Pro) forms a homodimer. In this study, using computational modelling, we identified residues at the NS2(Pro) dimer interface that have a role in dimerization and confirmed their capacity to influence dimerization by expression studies. Our modelling analysis identified 22 residues at the NS2(Pro) dimer interface that may be important for dimer formation. Based on the free binding energy, we selected the top five ranked mutations (V162A, M170A, I175A, D186A and I201A) for further st..

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University of Melbourne Researchers


Awarded by NHMRC

Funding Acknowledgements

We are grateful to Dr. T. Wakita for the pJFH1 plasmid. We also wish to thank Professor C. Rice for anti-NS5A mAb and Dr. A. Patel for anti-E2 mAb (AP33). The study was supported by grants from the Australian NHMRC and CASS. The HCV laboratory in the Burnet Institute is a member of ACH2. E. G. and G. T. were supported NHMRC Senior Research Fellowships 543139 and 543105, respectively, and P. A. R. was supported by NHMRC R. Douglas Wright Career Development Award 365209. The authors gratefully acknowledge the contribution of the Victorian Operational Infrastructure Support Program received by the Burnet Institute.