Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein

Re, Suyong; Mizuguchi, Kenji

The Journal of Physical Chemistry B, 2021, 125(8), 2089-2097

Number of Access:385（2025-12-10 13:28 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78921

Link to primary information 

File Format Terms of use Size Views Date.Available Description information
ms_jpcb_uslett_rev pdf None 3.58 MB 292 2022.02.19  
si_jpcb_uslett_rev pdf None 840 KB 98 2022.02.19 Supporting Information  

Item Information

Output File Export EndNote Basic Export Mendeley

Title
Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein
Creator
CreatorName
Re, Suyong
NRID
1000050450896 1000050450896
ORCID
0000-0003-3021-7078 0000-0003-3021-7078
researchmap permalink
kenji_mizuguchi kenji_mizuguchi
Scopus Author ID
57191477452 57191477452
CreatorName
Mizuguchi, Kenji
Description
This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry B, ©2021 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jpcb.0c11516.
Abstract
An understanding of how an antiviral monoclonal antibody recognizes its target is vital for the development of neutralizing antibodies and vaccines. The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility. Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response. The simulations attested to the variety of conformations and interactions of surface glycans. The results show that glycosylation nonuniformly shields the surface of the complex and only marginally affects protein dynamics. The glycans gather in distinct clusters through interaction with protein residues, and only a few regions are left accessible by an antibody. We successfully recovered known protein epitopes by integrating the simulation results with existing sequence- and structure-based epitope prediction methods. The results emphasize the rich structural environment of glycans and demonstrate that shielding is not merely envelopment by a uniform blanket of sugars. This work provides a molecular basis for integrating otherwise elusive structural properties of glycans into vaccine and neutralizing antibody developments.
Publisher
American Chemical Society
Source Title
The Journal of Physical Chemistry B
Volume (Issue)
125(8)
Page
2089-2097
Date of Issued
2021-02-19
Language
English
Handle URL
https://hdl.handle.net/11094/78921
PISSN
15206106
eISSN
15205207
NCID
AA11114073
Relation.isVersionOf
DOI (Publisher Version)
https://doi.org/10.1021/acs.jpcb.0c11516
Access Rights
open access
CopyRight
Copyright © 2021 American Chemical Society
oaire:version
Accepted Manuscript
Category
学術雑誌論文 Journal Article