| Item type |
文献 / Documents(1) |
| 公開日 |
2020-11-19 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.3389/fmicb.2016.00110 |
|
|
言語 |
ja |
|
|
関連名称 |
10.3389/fmicb.2016.00110 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
In silico Analysis of HIV-1 Env-gp120 Reveals Structural Bases for Viral Adaptation in Growth-Restrictive Cells |
|
言語 |
en |
| タイトル別表記 |
|
|
その他のタイトル |
Structural Modeling of HIV-1 Env-gp120 |
|
言語 |
en |
| 著者 |
ヨコヤマ, マサル
野間口, 雅子
土肥, 直哉
カンダ, タダヒト
足立, 昭夫
サトウ, ヒロノリ
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Variable V1/V2 and V3 loops on human immunodeficiency virus type 1 (HIV-1) envelope-gp120 core play key roles in modulating viral competence to recognize two infection receptors, CD4 and chemokine-receptors. However, molecular bases for the modulation largely remain unclear. To address these issues, we constructed structural models for a full-length gp120 in CD4-free and -bound states. The models showed topologies of gp120 surface loop that agree with those in reported structural data. Molecular dynamics simulation showed that in the unliganded state, V1/V2 loop settled into a thermodynamically stable arrangement near V3 loop for conformational masking of V3 tip, a potent neutralization epitope. In the CD4-bound state, however, V1/V2 loop was rearranged near the bound CD4 to support CD4 binding. In parallel, cell-based adaptation in the absence of anti-viral antibody pressures led to the identification of amino acid substitutions that individually enhance viral entry and growth efficiencies in association with reduced sensitivity to CCR5 antagonist TAK-779. Notably, all these substitutions were positioned on the receptors binding surfaces in V1/V2 or V3 loop. In silico structural studies predicted some physical changes of gp120 by substitutions with alterations in viral replication phenotypes. These data suggest that V1/V2 loop is critical for creating a gp120 structure that masks co-receptor binding site compatible with maintenance of viral infectivity, and for tuning a functional balance of gp120 between immune escape ability and infectivity to optimize HIV-1 replication fitness. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
homology modeling |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
MD simulation |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
V1/V2 loop |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
V3 loop |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
adaptive mutation |
| 書誌情報 |
en : Frontiers in Microbiology
巻 7,
p. 110,
発行日 2016-02-09
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1664302X |
| 出版者 |
|
|
出版者 |
Frontiers Media S.A. |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
Copyright ©2016 Yokoyama, Nomaguchi, Doi, Kanda, Adachi and Sato. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CCBY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| EID |
|
|
識別子 |
308188 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
fmicb_7_110.pdf (3.94 MB)
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