Article abstract
Nature Structural & Molecular Biology 15, 312 - 317 (2008)
Published online: 10 February 2008 | doi:10.1038/nsmb.1382
Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins
Shee-Mei Lok1, Victor Kostyuchenko1, Grant E Nybakken2, Heather A Holdaway1, Anthony J Battisti1, Soila Sukupolvi-Petty3, Dagmar Sedlak1,6, Daved H Fremont2, Paul R Chipman1, John T Roehrig4, Michael S Diamond2,3,5, Richard J Kuhn1 & Michael G Rossmann1
Abstract
The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 °C, suggesting that the virus is in dynamic motion making hidden epitopes briefly available. A cryo-electron microscope image reconstruction of the virus:Fab complex showed large changes in the organization of the E protein that exposed the epitopes on two of the three E molecules in each of the 60 icosahedral asymmetric units of the virus. The changes in the structure of the viral surface are presumably responsible for inhibiting attachment to cells.
- Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, Indiana 47907-2054, USA.
- Department of Pathology & Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
- Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
- Arbovirus Disease Branch, Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, P.O. Box 2087, Fort Collins, Colorado 80522, USA.
- Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
- Present address: Solid State Chemistry, An Aptuit Company, 3065 Kent Avenue, West Lafayette, Indiana 47906, USA.
Correspondence to: Michael G Rossmann1 e-mail: mr@purdue.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolaseNature Structural Biology Article (01 Dec 1997)
The structure of lactate dehydrogenase from Plasmodium falciparum reveals a new target for anti-malarial designNature Structural Biology Correspondence (01 Nov 1996)
Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transferNature Immunology Article (01 Oct 2001)
Structural basis of West Nile virus neutralization by a therapeutic antibodyNature Letters to Editor (29 Sep 2005)
See all 14 matches for Research
