SARS-CoV-2の融合ペプチドは,二層のミセルに挿入されたに再配置されます

Rama K Koppisetti¹, Yan G Fulcher¹, Steven R Van Doren^1,2

¹Department of Biochemistry, University of Missouri, Columbia, Missouri 65211 United States.

Journal of the American Chemical Society

|August 10, 2021

まとめ

SARS-CoV-2 融合ペプチドは細胞膜内での形をとり,ウイルスの侵入を容易にする. NMRによって明らかにされたこの構造の変化は,ウイルスを理解し,潜在的にブロックするために不可欠です.

科学分野:

バイオ物理学
構造生物学
ウイルス学

背景:

SARS-CoV-2のスパイク (S) タンパク質は,ウイルスと細胞膜を融合させ,ウイルスの侵入を媒介する.
Sタンパク質のタンパク質分解は,このプロセスに必要な融合ペプチドを含むS₂サブユニットを放出します.

研究の目的:

ウイルス細胞融合中のSARS-CoV-2 S₂融合ペプチドの構造と膜相互作用を解明する.
脂質二層に挿入した時の融合ペプチドの構成変化を理解する.

主な方法:

化学的シフト,¹⁵Nリラックス,および核オーバーハウザー効果 (NOE) 実験を含む核磁気共振 (NMR) スペクトロスコーピー.
ペプチドと膜の相互作用を研究するために,双層のミセルを膜模倣として利用した.

主要な成果:

融合ペプチドは溶液中の本質的に無秩序な状態から,膜内での安定した形構造へと移行する.
このケイジ構造は3つのヘリクから構成され,ヘリク1と2は水害性脂質の尾と相互作用し,ヘリク3は二重層から突出する.
構造は,プレフュージョン状態で観察された拡張形態と著しく異なる.

結論:

SARS-CoV-2 S₂融合ペプチドの決定された形構造は,ウイルス細胞膜融合のメカニズムに関する重要な洞察を提供します.
脂質との相互作用とCa2+イオンの結合の可能性は,膜不安定化と融合における役割を示唆している.
暴露されたヘリックス3は,抗体ベースの中和戦略の潜在的なターゲットです.

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