Functional and evolutionary insight from the crystal structure of rubella virus protein E1
| Autor: | M. Alejandra Tortorici, Marie-Christine Vaney, Thomas Krey, Félix A. Rey, Rana Al Kurdi, Rebecca M. DuBois, Giovanna Barba-Spaeth |
|---|---|
| Přispěvatelé: | Virologie Structurale, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was mainly funded by grant ANR-05-MIIM-012-02-Dentry to F.A.R., who also acknowledges support from Merck-Serono from the French Government’s Investissements d’Avenir program: Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Viral membrane fusion MESH: Hydrogen-Ion Concentration viruses Crystallography X-Ray medicine.disease_cause Membrane Fusion Viral Envelope Proteins MESH: Animals MESH: Evolution Molecular 0303 health sciences Multidisciplinary MESH: Protein Multimerization virus diseases Rubella virus Hydrogen-Ion Concentration Biological Evolution 3. Good health Rubella Infection Drosophila melanogaster Metals Viral evolution MESH: Models Molecular Viral protein Rubella Syndrome Congenital MESH: Rubella Syndrome Congenital MESH: Biological Evolution Biology MESH: Membrane Fusion Rubella Measles Cell Line MESH: Drosophila melanogaster Evolution Molecular 03 medical and health sciences medicine Animals [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Virus classification 030304 developmental biology X-ray crystallography Congenital rubella syndrome Binding Sites MESH: Metals 030306 microbiology medicine.disease MESH: Crystallography X-Ray Virology MESH: Cell Line MESH: Rubella virus MESH: Binding Sites MESH: Viral Envelope Proteins Liposomes MESH: Liposomes Protein Multimerization |
| Zdroj: | Nature Nature, 2013, 493 (7433), pp.552-556. ⟨10.1038/nature11741⟩ Nature, Nature Publishing Group, 2013, 493 (7433), pp.552-556. ⟨10.1038/nature11741⟩ |
| ISSN: | 0028-0836 1476-4687 1476-4679 |
| DOI: | 10.1038/nature11741⟩ |
| Popis: | International audience; Little is known about the three-dimensional organization of rubella virus, which causes a relatively mild measles-like disease in children but leads to serious congenital health problems when contracted in utero. Although rubella virus belongs to the same family as the mosquito-borne alphaviruses, in many respects it is more similar to other aerosol-transmitted human viruses such as the agents of measles and mumps. Although the use of the triple MMR (measles, mumps and rubella) live vaccine has limited its incidence in western countries, congenital rubella syndrome remains an important health problem in the developing world. Here we report the 1.8 Å resolution crystal structure of envelope glycoprotein E1, the main antigen and sole target of neutralizing antibodies against rubella virus. E1 is the main player during entry into target cells owing to its receptor-binding and membrane-fusion functions. The structure reveals the epitope and the neutralization mechanism of an important category of protecting antibodies against rubella infection. It also shows that rubella virus E1 is a class II fusion protein, which had hitherto only been structurally characterized for the arthropod-borne alphaviruses and flaviviruses. In addition, rubella virus E1 has an extensive membrane-fusion surface that includes a metal site, reminiscent of the T-cell immunoglobulin and mucin family of cellular proteins that bind phosphatidylserine lipids at the plasma membrane of cells undergoing apoptosis. Such features have not been seen in any fusion protein crystallized so far. Structural comparisons show that the class II fusion proteins from alphaviruses and flaviviruses, despite belonging to different virus families, are closer to each other than they are to rubella virus E1. This suggests that the constraints on arboviruses imposed by alternating cycles between vertebrates and arthropods resulted in more conservative evolution. By contrast, in the absence of this constraint, the strictly human rubella virus seems to have drifted considerably into a unique niche as sole member of the Rubivirus genus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|