TY - JOUR
T1 - Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins
AU - Lok, Shee Mei
AU - Kostyuchenko, Victor
AU - Nybakken, Grant E.
AU - Holdaway, Heather A.
AU - Battisti, Anthony J.
AU - Sukupolvi-Petty, Soila
AU - Sedlak, Dagmar
AU - Fremont, Daved H.
AU - Chipman, Paul R.
AU - Roehrig, John T.
AU - Diamond, Michael S.
AU - Kuhn, Richard J.
AU - Rossmann, Michael G.
N1 - Funding Information:
We thank K. Choi for help with the crystallography, W. Zhang for advice concerning the cryoEM reconstruction and P.G. Leiman for help in data collection. We also thank Argonne National Laboratory and the Advanced Photon Source (Argonne, Illinois, USA) staff at beamline GM/CA 23 for help and encouragement with diffraction data collection. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. The GM/CA CAT is funded by the US National Institute of General Medical Science (Y1-GM-1104) and the US National Cancer Institute (Y1-CO-1020). We thank S. Johnson for help with the sequencing of the 1A1D-2 VH and VL domains. The work was supported by the Pediatric Dengue Vaccine Initiative (TR-17) to R.J.K. and M.G.R. and a US National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases program project grant (AI055672) awarded to R.J.K., M.G.R. and others. M.S.D. and D.H.F. were supported by the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research (V54 A1057160). R.J.K. and M.G.R. also had support from Region V Great Lakes Regional Center of Excellence (NIH award U54 AI057153).
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=40949161794&partnerID=8YFLogxK
U2 - 10.1038/nsmb.1382
DO - 10.1038/nsmb.1382
M3 - Article
C2 - 18264114
AN - SCOPUS:40949161794
SN - 1545-9993
VL - 15
SP - 312
EP - 317
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 3
ER -