Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus.
Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the n-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown, partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables the formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable the determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.
['Yamamoto|Yuta|Y|', 'Nakano|Shogo|S|0000-0002-6614-7158', 'Seki|Fumio|F|', 'Shigeta|Yasuteru|Y|0000-0002-3219-6007', 'Ito|Sohei|S|', 'Tokiwa|Hiroaki|H|', 'Takeda|Makoto|M|0000-0002-8194-7727']
D000818:Animals D000080486:Computational Chemistry D004216:Distemper D004217:Distemper Virus, Canine D004283:Dog Diseases D004285:Dogs D006801:Humans D008251:Macaca D017354:Point Mutation D011485:Protein Binding D011991:Receptors, Virus D000071176:Signaling Lymphocytic Activation Molecule Family D013045:Species Specificity D013601:T-Lymphocytes
signaling lymphocytic activation molecule canine distemper virus molecular dynamics simulation fragment molecular orbital calculation