D614GのSARS-CoV-2スパイクタンパク質の構造と機能の分析
Leonid Yurkovetskiy1, Xue Wang2, Kristen E Pascal3
1Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Cell
|September 29, 2020
まとめ
SARS-CoV-2 D614G スパイクタンパク質の変種は,ウイルスの細胞への侵入を強めることで感染性を高めました. この変異体の構造の変化は,抗体中和に影響を与えることなく,ACE2結合と細胞融合を促進します.
科学分野:
- ウイルス学
- 構造生物学
- 分子生物学
背景:
- SARS-CoV-2のスパイク (S) タンパク質の変種D614Gは急速に世界的に支配的になりました.
- この変種の拡散を促す 分子メカニズムを理解することは 極めて重要です
研究 の 目的:
- SARS-CoV-2 D614Gスパイクタンパク質変種の感染性増加の機能的および構造的根拠を調査する.
- D614Gの感染性を様々な細胞タイプで祖先株と比較する.
主な方法:
- ヒトの肺や結腸の細胞,そしてACE2発現細胞の感染性アッセイ.
- スパイクタンパク質トリマーの冷凍電子顕微鏡検査
- ACE2結合親和性の生化学分析
主要な成果:
- D614G変種は,哺乳類のACE2オートログを発現する細胞モデルを含む,テストされた細胞モデルにおいて,感染性の強化を示した.
- Cryo-EMは,D614Gがスパイクトリマー構造を変化させ,ACE2結合と膜融合を好むことを明らかにした.
- ACE2結合率の低下は,より速い解離率によるものであったが,感染性は増加した.
- 受容体結合ドメインに対する抗体中和の効能は影響を受けなかった.
結論:
- D614G変異は,ACE2結合と細胞侵入に有利なよりオープンなスパイク構成を促進することによって,SARS-CoV-2の感染性を高めます.
- D614Gスパイクタンパク質の構造と機能の適応は,その急速な世界的な拡散を説明します.
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