9KRF

Alpha-hemolysin heptameric pore state bound to 10:0 PC lipid chains derived from 10:0 PC liposomes

9KRF の概要

• エントリーDOI: 10.2210/pdb9krf/pdb
• EMDBエントリー: 62310
• 分子名称: Alpha-hemolysin, 1,2-DIDECANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE (2 entities in total)
• 機能のキーワード: pft, liposomes, lipid binding protein
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 236997.10

構造登録者

Chatterjee, A.,Roy, A.,Dutta, S. (登録日: 2024-11-27, 公開日: 2025-06-11, 最終更新日: 2025-07-23)

主引用文献

Chatterjee, A.,Roy, A.,Satheesh, T.,Das, P.P.,Mondal, B.,Kishore, P.,Ganji, M.,Dutta, S.
Structural insights into pre-pore intermediates of alpha-hemolysin in the lipidic environment.
Nat Commun, 16:6348-6348, 2025

PubMed Abstract: The infectious microbe Staphylococcus aureus releases an array of cytotoxic pore-forming toxins (PFTs) that severely damage the cell membrane during bacterial infection. However, the interaction interfaces between the host cell membrane and toxin were hardly explored. So far, there are no pore, and intermediate structures of these toxins available in the presence of bio-membrane, which could elucidate the pore-forming mechanism. Here, we investigate the structure of different conformational states of this alpha-hemolysin (α-HL/Hla), a β-PFT in lipidic environment using single-particle cryo-EM. Additionally, we explore lipid destabilization by the toxin, using single-molecule imaging, confocal imaging, and validation of lipid-protein interactions using mutational studies. We elucidate eight cryo-EM structures of wildtype α-HL with various liposomes, which are composed of either 10:0 PC or Egg-PC/Cholesterol or Egg-PC/Sphingomyelin or 10:0 PC/Sphingomyelin. Our structural and biophysical studies confirm that different chain lengths and various membrane compositions facilitate the formation of intermediate pre-pores and complete pore species. We also demonstrate that the percentage of pre-pore population increases due to sphingomyelin-induced membrane rigidity. Altogether, this study unveils the structure-function analysis of the pre-pore to pore transition of wildtype α-HL during its crosstalk with the lipid membrane.

PubMed: 40640160
DOI: 10.1038/s41467-025-61741-x

実験手法

ELECTRON MICROSCOPY (2.8 Å)