Structural Transition and Antibody Binding of EBOV GP and ZIKV E Proteins from Pre-Fusion to Fusion-Initiation State
Abstract
Membrane fusion proteins are responsible for viral entry into host cells—a crucial first step in viral infection. Additonally, these proteins undergo large conformational changes from pre-fusion to fusion-initiation structures, and, despite differences in viral genomes and disease etiology, many fusion proteins are arranged as trimers. Structural information for both pre-fusion and fusion-initiation states is critical for understanding virus neutralization by the host immune system. In the case of Ebola virus glycoprotein (EBOV GP) and Zika virus envelope protein (ZIKV E), pre-fusion state structures have been identified experimentally, but only partial structures of fusion-initiation states have been described. While the fusion-initiation structure is in an energetically unfavorable state that is difficult to solve experimentally, the existing structural information combined with computational approaches enabled the modeling of fusion-initiation state structures of both proteins. In conclusion, these structural models provide an improved understanding of four different neutralizing antibodies in the prevention of viral host entry.
- Authors:
-
[1];
[2];
[1];
[1];
[1];
[1];
[1]
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos, NM (United States)
- Univ. of Georgia, Athens, GA (United States)
- Publication Date:
- Research Org.:
- lanl; Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Laboratory Directed Research and Development (LDRD) Program
- OSTI Identifier:
- 1477648
- Report Number(s):
- LA-UR-17-24395
Journal ID: ISSN 2218-273X; BIOMHC
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Biomolecules
- Additional Journal Information:
- Journal Volume: 8; Journal Issue: 2; Journal ID: ISSN 2218-273X
- Publisher:
- MDPI
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; EBOV GP; ZIKV E; pre-fusion-to-fusion transition; antibody binding
Citation Formats
Lappala, Anna, Nishima, Wataru, Miner, Jacob Carlson, Fenimore, Paul W., Fischer, William Mclean, Hraber, Peter Thomas, Zhang, Ming, McMahon, Benjamin, and Tung, Chang-Shung. Structural Transition and Antibody Binding of EBOV GP and ZIKV E Proteins from Pre-Fusion to Fusion-Initiation State. United States: N. p., 2018.
Web. doi:10.3390/biom8020025.
Lappala, Anna, Nishima, Wataru, Miner, Jacob Carlson, Fenimore, Paul W., Fischer, William Mclean, Hraber, Peter Thomas, Zhang, Ming, McMahon, Benjamin, & Tung, Chang-Shung. Structural Transition and Antibody Binding of EBOV GP and ZIKV E Proteins from Pre-Fusion to Fusion-Initiation State. United States. https://doi.org/10.3390/biom8020025
Lappala, Anna, Nishima, Wataru, Miner, Jacob Carlson, Fenimore, Paul W., Fischer, William Mclean, Hraber, Peter Thomas, Zhang, Ming, McMahon, Benjamin, and Tung, Chang-Shung. Thu .
"Structural Transition and Antibody Binding of EBOV GP and ZIKV E Proteins from Pre-Fusion to Fusion-Initiation State". United States. https://doi.org/10.3390/biom8020025. https://www.osti.gov/servlets/purl/1477648.
@article{osti_1477648,
title = {Structural Transition and Antibody Binding of EBOV GP and ZIKV E Proteins from Pre-Fusion to Fusion-Initiation State},
author = {Lappala, Anna and Nishima, Wataru and Miner, Jacob Carlson and Fenimore, Paul W. and Fischer, William Mclean and Hraber, Peter Thomas and Zhang, Ming and McMahon, Benjamin and Tung, Chang-Shung},
abstractNote = {Membrane fusion proteins are responsible for viral entry into host cells—a crucial first step in viral infection. Additonally, these proteins undergo large conformational changes from pre-fusion to fusion-initiation structures, and, despite differences in viral genomes and disease etiology, many fusion proteins are arranged as trimers. Structural information for both pre-fusion and fusion-initiation states is critical for understanding virus neutralization by the host immune system. In the case of Ebola virus glycoprotein (EBOV GP) and Zika virus envelope protein (ZIKV E), pre-fusion state structures have been identified experimentally, but only partial structures of fusion-initiation states have been described. While the fusion-initiation structure is in an energetically unfavorable state that is difficult to solve experimentally, the existing structural information combined with computational approaches enabled the modeling of fusion-initiation state structures of both proteins. In conclusion, these structural models provide an improved understanding of four different neutralizing antibodies in the prevention of viral host entry.},
doi = {10.3390/biom8020025},
journal = {Biomolecules},
number = 2,
volume = 8,
place = {United States},
year = {Thu May 10 00:00:00 EDT 2018},
month = {Thu May 10 00:00:00 EDT 2018}
}
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Works referencing / citing this record:
Real-Time Analysis of Individual Ebola Virus Glycoproteins Reveals Pre-Fusion, Entry-Relevant Conformational Dynamics
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- Durham, Natasha D.; Howard, Angela R.; Govindan, Ramesh
- Viruses, Vol. 12, Issue 1