Functional and evolutionary insight from the crystal structure of rubella virus protein E1

• Published in: Nature (London) 2013-01, Vol.493 (7433), p.552-556
• Main Authors: DuBois, Rebecca M., Vaney, Marie-Christine, Tortorici, M. Alejandra, Kurdi, Rana Al, Barba-Spaeth, Giovanna, Krey, Thomas, Rey, Félix A.
• Format: Article
• Language: English
• Subjects: 631/326/596/2116; 631/326/596/2554; 631/535/1266; Animals; Arthropoda; Binding Sites; Biochemistry; Biochemistry, Molecular Biology; Biological Evolution; Carbonyl compounds; Cell Line; Crystal structure; Crystallography, X-Ray; Crystals; Drosophila melanogaster; Evolution, Molecular; Health aspects; Humanities and Social Sciences; Hydrogen-Ion Concentration; Insects; letter; Life Sciences; Liposomes; Liposomes - chemistry; Liposomes - metabolism; Membrane Fusion; Metals; Metals - metabolism; Models, Molecular; multidisciplinary; Natural history; Physiological aspects; Protein Multimerization; Proteins; Rubella; Rubella Syndrome, Congenital; Rubella Syndrome, Congenital - virology; Rubella virus; Rubella virus - chemistry; Rubella virus - physiology; Rubivirus; Science; Structure; Studies; Viral Envelope Proteins; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; Viral Envelope Proteins - ultrastructure; Viral proteins
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature11741

The crystal structure of rubella virus E1 glycoprotein in its post-fusion form reveals a class II fusion protein with distinct features so far unseen in any other crystallized fusion protein; the location of an antibody-neutralization epitope also suggests that rubella-specific antibodies may function through prevention of E1 glycoprotein trimer formation during cell entry. Rubella virus envelope glycoprotein structure The rubella virus causes the relatively mild 'German' or three-day measles in children but leads to serious congenital health problems when contracted in utero . Live vaccine has limited the incidence in western countries, but congenital rubella syndrome remains an important health problem in the developing world. Flix Rey et al . have determined the crystal structure of the rubella virus envelope glycoprotein E1. It has class II architecture and a membrane-fusion surface with a metal-binding site. The structure indicates that the rubella virus E1 glycoprotein evolved to become distant from that of the mosquito-borne viruses in the same family, creating its own niche as a strictly human virus. This has interesting parallels with the similarly strictly human hepatitis C virus, which belongs to the same family as the mosquito-borne flaviviruses. 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 1 . 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 an