1ztx
From Proteopedia
(New page: 200px<br /> <applet load="1ztx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ztx, resolution 2.500Å" /> '''West Nile Virus En...) |
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| - | [[Image:1ztx.gif|left|200px]]<br /> | + | [[Image:1ztx.gif|left|200px]]<br /><applet load="1ztx" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ztx" size=" | + | |
caption="1ztx, resolution 2.500Å" /> | caption="1ztx, resolution 2.500Å" /> | ||
'''West Nile Virus Envelope Protein DIII in complex with neutralizing E16 antibody Fab'''<br /> | '''West Nile Virus Envelope Protein DIII in complex with neutralizing E16 antibody Fab'''<br /> | ||
==Overview== | ==Overview== | ||
| - | West Nile virus is a mosquito-borne flavivirus closely related to the | + | West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop. Humoral immunity has an essential protective function early in the course of West Nile virus infection. Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. Structurally, the E16 antibody Fab fragment engages 16 residues positioned on four loops of DIII, a consensus neutralizing epitope sequence conserved in West Nile virus and distinct in other flaviviruses. The E16 epitope protrudes from the surface of mature virions in three distinct environments, and docking studies predict Fab binding will leave five-fold clustered epitopes exposed. We also show that E16 inhibits infection primarily at a step after viral attachment, potentially by blocking envelope glycoprotein conformational changes. Collectively, our results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZTX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/West_nile_virus West nile virus]. Full crystallographic information is available from [http:// | + | 1ZTX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/West_nile_virus West nile virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZTX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: West nile virus]] | [[Category: West nile virus]] | ||
| - | [[Category: Diamond, M | + | [[Category: Diamond, M S.]] |
| - | [[Category: Fremont, D | + | [[Category: Fremont, D H.]] |
| - | [[Category: Nybakken, G | + | [[Category: Nybakken, G E.]] |
[[Category: Oliphant, T.]] | [[Category: Oliphant, T.]] | ||
[[Category: antibody]] | [[Category: antibody]] | ||
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[[Category: virus]] | [[Category: virus]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:19:01 2008'' |
Revision as of 14:19, 21 February 2008
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West Nile Virus Envelope Protein DIII in complex with neutralizing E16 antibody Fab
Overview
West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop. Humoral immunity has an essential protective function early in the course of West Nile virus infection. Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. Structurally, the E16 antibody Fab fragment engages 16 residues positioned on four loops of DIII, a consensus neutralizing epitope sequence conserved in West Nile virus and distinct in other flaviviruses. The E16 epitope protrudes from the surface of mature virions in three distinct environments, and docking studies predict Fab binding will leave five-fold clustered epitopes exposed. We also show that E16 inhibits infection primarily at a step after viral attachment, potentially by blocking envelope glycoprotein conformational changes. Collectively, our results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases.
About this Structure
1ZTX is a Single protein structure of sequence from Mus musculus and West nile virus. Full crystallographic information is available from OCA.
Reference
Structural basis of West Nile virus neutralization by a therapeutic antibody., Nybakken GE, Oliphant T, Johnson S, Burke S, Diamond MS, Fremont DH, Nature. 2005 Sep 29;437(7059):764-9. PMID:16193056
Page seeded by OCA on Thu Feb 21 16:19:01 2008
Categories: Mus musculus | Single protein | West nile virus | Diamond, M S. | Fremont, D H. | Nybakken, G E. | Oliphant, T. | Antibody | Envelope | Fab | Neutralizing | Virus
