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)

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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.