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The flavivirus envelope protein is the dominant antigen in eliciting neutralizing antibodies and plays an important role in inducing immunologic responses in the infected host.We have determined the solution structures of the major antigenic domain (domain Ⅲ) of the Japanese Encephalitis Virus (JEV) and Dengue Virus (DENV) envelope proteins.Domain Ⅲ forms a β-barrel type structure composed of six antiparallel β-strands resembling the immunoglobulin constant domain.We have also identified epitopes of the domain Ⅲ to its neutralizing antibody and to heparin by chemical shift perturbations.Site-directed mutagenesis experiments are performed to confLrrn the NMR results.Our study provides a structural basis for understanding the mechanism of immunologic protection and for rational design of vaccines and heparin based inhibitors effective against flaviviruses.(NSC93-2113-B-007-020 and NS C94-2311-B-007-007).