9CTW

Cryo-EM structure of SARS-CoV-2 M (long conformation) in the presence of C1P

9CTW の概要

• エントリーDOI: 10.2210/pdb9ctw/pdb
• 関連するPDBエントリー: 9CTU
• EMDBエントリー: 45919 45921
• 分子名称: Long conformation Fab light chain, Long conformation Fab heavy chain, Membrane protein (3 entities in total)
• 機能のキーワード: sars-cov-2, coronavirus, viral protein, capsid protein, membrane protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 161663.61

構造登録者

Dolan, K.A.,Brohawn, S.G. (登録日: 2024-07-25, 公開日: 2024-11-06, 最終更新日: 2025-05-14)

主引用文献

Dutta, M.,Dolan, K.A.,Amiar, S.,Bass, E.J.,Sultana, R.,Voth, G.A.,Brohawn, S.G.,Stahelin, R.V.
Direct lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly.
Biorxiv, 2024

PubMed Abstract: M is the most abundant structural membrane protein in coronaviruses and is essential for the formation of infectious virus particles. SARS-CoV-2 M adopts two conformations, M and M, and regulated transition between states is hypothesized to coordinate viral assembly and budding. However, the factors that regulate M conformation and roles for each state are unknown. Here, we discover a direct M-sphingolipid interaction that controls M conformational dynamics and virus assembly. We show M binds Golgi-enriched anionic lipids including ceramide-1-phosphate (C1P). Molecular dynamics simulations show C1P interaction promotes a long to short transition and energetically stabilizes M. Cryo-EM structures show C1P specifically binds M at a conserved site bridging transmembrane and cytoplasmic regions. Disrupting M-C1P interaction alters M subcellular localization, reduces interaction with Spike and E, and impairs subsequent virus-like particle cell entry. Together, these results show endogenous signaling lipids regulate M structure and support a model in which M is stabilized in the early endomembrane system to organize other structural proteins prior to viral budding.

PubMed: 39574576
DOI: 10.1101/2024.11.04.620124

実験手法

ELECTRON MICROSCOPY (3.01 Å)