Structural basis of the interactions between tyrosine kinase c-Src and the Hepatitis C virus proteins NS5A and NS5B, and their influence on liver damage and regeneration (A11)

• Subject Area: Biophysics
• Term: from 2012 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190586431

In HCV infected cells tyrosine kinase c-Src, which is important for regulation of cell growth and differentiation, is recruited into the viral replication machinery by the HCV proteins NS5A and -B. The intrinsically disordered character and tyrosine-phosphorylation of NS5A seems to be crucial for NS5A/B/ c-Src complex formation. Our results demonstrate canonical SH2- and SH3- as well as non-canonical SH3-binding of NS5A with c-Src, but no direct NS5B/ c-Src interaction. Our focus now lies on the establishment of complex reconstitution in nanodiscs and its structural analysis. Specific inhibitors of complex formation will help to understand how NS5A and -B influence normal c-Src functions.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 974: Communication and System Relevance in Liver Injury and Regeneration
• Applicant Institution: Heinrich-Heine-Universität Düsseldorf
• Project Head: Professor Dieter Willbold, Ph.D.