title: Insight into structural diversity of influenza virus haemagglutinin.
abstract: Influenza virus infects host cells through membrane fusion, a process mediated by the low pH-induced conformational change of the viral surface glycoprotein haemagglutinin (HA). We determined the structures and biochemical properties of the HA proteins from A/Korea/01/2009 (KR01), a 2009 pandemic strain, and A/Thailand/CU44/2006 (CU44), a seasonal strain. The crystal structure of KR01 HA revealed a V-shaped head-to-head arrangement, which is not seen in other HA proteins including CU44 HA. We isolated a broadly neutralizing H1-specific monoclonal antibody GC0757. The KR01 HA-Fab0757 complex structure also exhibited a head-to-head arrangement of HA. Both native and Fab complex structures reveal a different spatial orientation of HA1 relative to HA2, indicating that HA is flexible and dynamic at neutral pH. Further, the KR01 HA exhibited significantly lower protein stability and increased susceptibility to proteolytic cleavage compared with other HAs. Our structures provide important insights into the conformational flexibility of HA.
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Ki Joon
authors: KJ
authors: Cho
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Ji-Hye
authors: JH
authors: Lee
authors: Antibody Engineering Laboratory, Central Research Center, Green Cross Corp., Yongin Kyunggi 446-799, Korea.
authors: Kwang W
authors: KW
authors: Hong
authors: Antibody Engineering Laboratory, Central Research Center, Green Cross Corp., Yongin Kyunggi 446-799, Korea.
authors: Se-Ho
authors: SH
authors: Kim
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Yiho
authors: Y
authors: Park
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Jun Young
authors: JY
authors: Lee
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Seokha
authors: S
authors: Kang
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Sella
authors: S
authors: Kim
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Ji Hoon
authors: JH
authors: Yang
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Eui-Ki
authors: EK
authors: Kim
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Jong Hyeon
authors: JH
authors: Seok
authors: Protein Design Laboratory, Yokohama City University, Yokohama 230-0045, Japan.
authors: Satoru
authors: S
authors: Unzai
authors: Protein Design Laboratory, Yokohama City University, Yokohama 230-0045, Japan.
authors: Sam Yong
authors: SY
authors: Park
authors: Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.|Department for Molecular Biomedical Research, VIB, 9052 Ghent, Belgium.
authors: Xavier
authors: X
authors: Saelens
authors: College of Veterinary Medicine, Chungnam National University, DaeJeon 305-764, Korea.
authors: Chul-Joong
authors: CJ
authors: Kim
authors: Influenza Virus Team, Center for Infectious Diseases, Korea Centers for Disease Control and Prevention, Osong Chungbuk 363-951, Korea.
authors: Joo-Yeon
authors: JY
authors: Lee
authors: Influenza Virus Team, Center for Infectious Diseases, Korea Centers for Disease Control and Prevention, Osong Chungbuk 363-951, Korea.
authors: Chun
authors: C
authors: Kang
authors: Influenza Virus Team, Center for Infectious Diseases, Korea Centers for Disease Control and Prevention, Osong Chungbuk 363-951, Korea.
authors: Hee-Bok
authors: HB
authors: Oh
authors: Department of Food and Nutrition, Duksung Women's University, Seoul 132-714, Korea.
authors: Mi Sook
authors: MS
authors: Chung
authors: Department of Biotechnology & Bioinformatics, College of Science & Technology, Korea University, Sejong 339-700, Korea.
authors: Kyung Hyun
authors: KH
authors: Kim
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000276:immunology / Q000302:isolation & purification; D018360:Crystallography, X-Ray; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D009975:Orthomyxoviridae / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D055550:Protein Stability; D059748:Proteolysis
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus