Probing the Interactions Between U24 from HHV-6A/7 and Fyn-SH3 or WW Domain Proteins

U24 is a type II tail-anchored putative membrane protein unique to the Roseolovirus family, including HHV-6 and HHV-7. It contains an N-terminal proline-rich region and is believed to function by disrupting the signalling pathway in order to ensure the virus' survival. HHV-6A is a neurovirulent virus as it is often found in multiple sclerosis (MS) patients. It has also been shown to directly induce demyelination, a typical MS symptom, in naive adult marmosets1. U24 from HHV-6A shares a seven residue identity with myelin basic protein (MBP), a protein responsible for the compaction of the myelin sheath in the CNS2. U24 from HHV-7, on the other hand, does not share this sequence identity with MBP, but this virus has also been implicated in MS, though indirectly3.In order to elucidate the exact role of U24 in MS, we have investigated the interaction of this protein with other partners such as the SH3 domain from Fyn tyrosine kinase and WW domain proteins. GST pull-downs, NMR titration data and molecular dynamics simulations will be presented. The differences in binding observed for U24 from HHV-6A and -7 will shed light into the hypothesis that U24 may function by mimicking MBP, as it has been previously shown that U24 and MBP can be phosphorylated in a similar manner4.References1. Genain, C. (2006). US 2006/0130161 A1.2. Harauz, G., Ladizhansky, V., and Boggs, J.M. (2009). Biochemistry 48, 8094–8104.3. Sullivan, B.M., and Coscoy, L. (2010). Journal of Virology 84, 1265–1275.4. Tait, A.R., and Straus, S.K. (2008). FEBS Letters 582, 2685–2688.