Abstract
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 β-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.
| Original language | English |
|---|---|
| Pages (from-to) | 19535-19540 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 104 |
| Issue number | 49 |
| DOIs | |
| Publication status | Published - Dec 4 2007 |
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All Science Journal Classification (ASJC) codes
- Genetics
- General
Cite this
Crystal structure of measles virus hemagglutinin provides insight into effective vaccines. / Hashiguchi, Takao; Kajikawa, Mizuho; Maita, Nobuo; Takeda, Makoto; Kuroki, Kimiko; Tabata, Kaori; Kohda, Daisuke; Yanagi, Yusuke; Maenaka, Katsumi.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 49, 04.12.2007, p. 19535-19540.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Crystal structure of measles virus hemagglutinin provides insight into effective vaccines
AU - Hashiguchi, Takao
AU - Kajikawa, Mizuho
AU - Maita, Nobuo
AU - Takeda, Makoto
AU - Kuroki, Kimiko
AU - Tabata, Kaori
AU - Kohda, Daisuke
AU - Yanagi, Yusuke
AU - Maenaka, Katsumi
PY - 2007/12/4
Y1 - 2007/12/4
N2 - 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 β-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.
AB - 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 β-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.
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U2 - 10.1073/pnas.0707830104
DO - 10.1073/pnas.0707830104
M3 - Article
VL - 104
SP - 19535
EP - 19540
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 49
ER -