Crystal structure of measles virus hemagglutinin provides insight into effective vaccines.
Measles still remains a major cause of childhood morbidity and mortality worldwide. Measles virus (MV) vaccines are highly successful, but the mechanism underlying their efficacy has been unclear. Here we report the crystal structure of the MV attachment protein, hemagglutinin, responsible for MV entry. The receptor-binding head domain exhibits a cubic-shaped beta-propeller structure and forms a homodimer. N-linked sugars appear to mask the broad regions and cause the two molecules forming the dimer to tilt oppositely toward the horizontal plane. Accordingly, residues of the putative receptor-binding site, highly conserved among MV strains, are strategically positioned in the unshielded area of the protein. These conserved residues also serve as epitopes for neutralizing antibodies, ensuring the serological monotype, a basis for effective MV vaccines. Our findings suggest that sugar moieties in the MV hemagglutinin critically modulate virus-receptor interaction as well as antiviral antibody responses, differently from sugars of the HIV gp120, which allow for immune evasion.
Hashiguchi
Takao
T
Department of Virology, Faculty of Medicine, and Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
Kajikawa
Mizuho
M
Maita
Nobuo
N
Takeda
Makoto
M
Kuroki
Kimiko
K
Sasaki
Kaori
K
Kohda
Daisuke
D
Yanagi
Yusuke
Y
Maenaka
Katsumi
K
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology; D000998:Antiviral Agents / Q000737:chemistry; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D015195:Drug Design; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D008458:Measles Vaccine / Q000276:immunology*; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology; D011991:Receptors, Virus / Q000737:chemistry; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D000998:Antiviral Agents; D002241:Carbohydrates; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D014764:Viral Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019158:N-Acetylneuraminic Acid