Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein.
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 structure of the major antigenic domain (domain III) of the Japanese encephalitis virus (JEV) envelope protein. The JEV domain III forms a beta-barrel type structure composed of six antiparallel beta-strands resembling the immunoglobulin constant domain. We have also identified epitopes of the JEV domain III to its neutralizing antibody by chemical shift perturbation measurements. Site-directed mutagenesis experiments are performed to confirm the NMR results. Our study provides a structural basis for understanding the mechanism of immunologic protection and for rational design of vaccines effective against flaviviruses.
Wu
Kuen-Phon
KP
Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan 300, Republic of China.
Wu
Chih-Wei
CW
Tsao
Ya-Ping
YP
Kuo
Ting-Wei
TW
Lou
Yuan-Chao
YC
Lin
Cheng-Wen
CW
Wu
Suh-Chin
SC
Cheng
Jya-Wei
JW
D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000737:chemistry; D004664:Encephalitis Virus, Japanese / Q000378:metabolism*; D000939:Epitopes; D005416:Flavivirus / Q000737:chemistry* / Q000378:metabolism; D015686:Gene Products, env / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000941:Antigens; D000939:Epitopes; D015686:Gene Products, env