West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody

Bärbel Kaufmann; Grant E. Nybakken; Paul R. Chipman; Wei Zhang; Michael S. Diamond; Daved H. Fremont; Richard J. Kuhn; Michael G. Rossmann

doi:10.1073/pnas.0603488103

West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody

Bärbel Kaufmann, Grant E. Nybakken, Paul R. Chipman, Wei Zhang, Michael S. Diamond, Daved H. Fremont, Richard J. Kuhn, Michael G. Rossmann

Diagnostic and Biological Sciences

Research output: Contribution to journal › Article › peer-review

114 Scopus citations

Abstract

Flaviviruses, such as West Nile virus (WNV), are significant human pathogens. The humoral immune response plays an important role in the control of flavivirus infection and disease. The structure of WNV complexed with the Fab fragment of the strongly neutralizing mAb E16 was determined to 14.5-Å resolution with cryo-electron microscopy. E16, an antibody with therapeutic potential, binds to domain III of the WNV envelope glycoprotein. Because of steric hindrance, Fab E16 binds to only 120 of the 180 possible binding sites on the viral surface. Fitting of the previously determined x-ray structure of the Fab-domain III complex into the cryo-electron microscopy density required a change of the elbow angle between the variable and constant domains of the Fab. The structure suggests that the E1G antibody neutralizes WNV by blocking the initial rearrangement of the E glycoprotein before fusion with a cellular membrane.

Original language	English (US)
Pages (from-to)	12400-12404
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	103
Issue number	33
DOIs	https://doi.org/10.1073/pnas.0603488103
State	Published - Aug 15 2006

Keywords

Cryo-electron microscopy
Flavivirus
Neutralization

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10.1073/pnas.0603488103

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title = "West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody",

abstract = "Flaviviruses, such as West Nile virus (WNV), are significant human pathogens. The humoral immune response plays an important role in the control of flavivirus infection and disease. The structure of WNV complexed with the Fab fragment of the strongly neutralizing mAb E16 was determined to 14.5-{\AA} resolution with cryo-electron microscopy. E16, an antibody with therapeutic potential, binds to domain III of the WNV envelope glycoprotein. Because of steric hindrance, Fab E16 binds to only 120 of the 180 possible binding sites on the viral surface. Fitting of the previously determined x-ray structure of the Fab-domain III complex into the cryo-electron microscopy density required a change of the elbow angle between the variable and constant domains of the Fab. The structure suggests that the E1G antibody neutralizes WNV by blocking the initial rearrangement of the E glycoprotein before fusion with a cellular membrane.",

keywords = "Cryo-electron microscopy, Flavivirus, Neutralization",

author = "B{\"a}rbel Kaufmann and Nybakken, {Grant E.} and Chipman, {Paul R.} and Wei Zhang and Diamond, {Michael S.} and Fremont, {Daved H.} and Kuhn, {Richard J.} and Rossmann, {Michael G.}",

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T1 - West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody

AU - Kaufmann, Bärbel

AU - Nybakken, Grant E.

AU - Chipman, Paul R.

AU - Zhang, Wei

AU - Diamond, Michael S.

AU - Fremont, Daved H.

AU - Kuhn, Richard J.

AU - Rossmann, Michael G.

PY - 2006/8/15

Y1 - 2006/8/15

N2 - Flaviviruses, such as West Nile virus (WNV), are significant human pathogens. The humoral immune response plays an important role in the control of flavivirus infection and disease. The structure of WNV complexed with the Fab fragment of the strongly neutralizing mAb E16 was determined to 14.5-Å resolution with cryo-electron microscopy. E16, an antibody with therapeutic potential, binds to domain III of the WNV envelope glycoprotein. Because of steric hindrance, Fab E16 binds to only 120 of the 180 possible binding sites on the viral surface. Fitting of the previously determined x-ray structure of the Fab-domain III complex into the cryo-electron microscopy density required a change of the elbow angle between the variable and constant domains of the Fab. The structure suggests that the E1G antibody neutralizes WNV by blocking the initial rearrangement of the E glycoprotein before fusion with a cellular membrane.

AB - Flaviviruses, such as West Nile virus (WNV), are significant human pathogens. The humoral immune response plays an important role in the control of flavivirus infection and disease. The structure of WNV complexed with the Fab fragment of the strongly neutralizing mAb E16 was determined to 14.5-Å resolution with cryo-electron microscopy. E16, an antibody with therapeutic potential, binds to domain III of the WNV envelope glycoprotein. Because of steric hindrance, Fab E16 binds to only 120 of the 180 possible binding sites on the viral surface. Fitting of the previously determined x-ray structure of the Fab-domain III complex into the cryo-electron microscopy density required a change of the elbow angle between the variable and constant domains of the Fab. The structure suggests that the E1G antibody neutralizes WNV by blocking the initial rearrangement of the E glycoprotein before fusion with a cellular membrane.

KW - Cryo-electron microscopy

KW - Flavivirus

KW - Neutralization

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U2 - 10.1073/pnas.0603488103

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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

IS - 33

ER -

West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody

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