4P24

pore forming toxin

4P24 の概要

• エントリーDOI: 10.2210/pdb4p24/pdb
• 関連するPDBエントリー: 4P1X 4P1Y
• 分子名称: Alpha-hemolysin, (4S)-2-METHYL-2,4-PENTANEDIOL (2 entities in total)
• 機能のキーワード: pore forming toxin, toxin
• 由来する生物種: Staphylococcus aureus subsp. aureus Mu50
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 241672.08

構造登録者

Sugawara, T.,Yamashita, D.,Tanaka, Y.,Tanaka, I.,Yao, M. (登録日: 2014-03-01, 公開日: 2015-03-11, 最終更新日: 2023-12-27)

主引用文献

Sugawara, T.,Yamashita, D.,Kato, K.,Peng, Z.,Ueda, J.,Kaneko, J.,Kamio, Y.,Tanaka, Y.,Yao, M.
Structural basis for pore-forming mechanism of staphylococcal alpha-hemolysin.
Toxicon, 108:226-231, 2015

PubMed Abstract: Staphylococcal α-hemolysin (α-HL) is a β-barrel pore-forming toxin (PFT) expressed by Staphylococcus aureus. α-HL is secreted as a water-soluble monomeric protein, which binds to target membranes and forms membrane-inserted heptameric pores. To explore the pore-forming mechanism of α-HL in detail, we determined the crystal structure of the α-HL monomer and prepore using H35A mutant and W179A/R200A mutant, respectively. Although the overall structure of the monomer was similar to that of other staphylococcal PFTs, a marked difference was observed in the N-terminal amino latch, which bent toward the prestem. Moreover, the prestem was fastened by the cap domain with a key hydrogen bond between Asp45 and Tyr118. Prepore structure showed that the transmembrane region is roughly formed with flexibility, although the upper half of the β-barrel is formed appropriately. Structure comparison among monomer, prepore and pore revealed a series of motions, in which the N-terminal amino latch released upon oligomerization destroys its own key hydrogen bond between Asp45-Tyr118. This action initiated the protrusion of the prestem. Y118F mutant and the N-terminal truncated mutant markedly decreased in the hemolytic activity, indicating the importance of the key hydrogen bond and the N-terminal amino latch on the pore formation. Based on these observations, we proposed a dynamic molecular mechanism of pore formation for α-HL.

PubMed: 26428390
DOI: 10.1016/j.toxicon.2015.09.033

実験手法

X-RAY DIFFRACTION (3.1 Å)