Probing the Interaction between U24 and the SH3 Domain of Fyn Tyrosine Kinase

The putative membrane protein U24 from HHV-6A shares a seven-residue sequence identity (which includes a PxxP motif) with myelin basic protein (MBP), a protein responsible for the compaction of the myelin sheath in the central nervous system. U24 from HHV-6A also shares a PPxY motif with U24 from the related virus HHV-7, allowing them both to block early endosomal recycling. Recently, MBP has been shown to have protein-protein interactions with a range of proteins, including proteins containing SH3 domains. Given that this interaction is mediated by the proline-rich segment in MBP, and that similar proline-rich segments are found in U24, we investigate here whether U24 also interacts with SH3 domain-containing proteins and what the nature of that interaction might be. The implications of a U24-Fyn tyrosine kinase SH3 domain interaction are discussed in terms of the hypothesis that U24 may function like MBP through molecular mimicry, potentially contributing to the disease state of multiple sclerosis or other demyelinating disorders.