4OW6

Crystal structure of Diphtheria Toxin at acidic pH

4OW6 の概要

• エントリーDOI: 10.2210/pdb4ow6/pdb
• 分子名称: Diphtheria toxin (1 entity in total)
• 機能のキーワード: diphtheria toxin translocation, membrane insertion, bicelles, membrane channels, toxin, transferase
• 由来する生物種: Corynebacterium diphtheriae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116822.72

構造登録者

Leka, O.,Vallese, F.,Pirazzini, M.,Berto, P.,Montecucco, C.,Zanotti, G. (登録日: 2014-01-31, 公開日: 2014-04-02, 最終更新日: 2024-10-23)

主引用文献

Leka, O.,Vallese, F.,Pirazzini, M.,Berto, P.,Montecucco, C.,Zanotti, G.
Diphtheria toxin conformational switching at acidic pH.
Febs J., 281:2115-2122, 2014

PubMed Abstract: Diphtheria toxin (DT), the etiological agent of the homonymous disease, like other bacterial toxins, has to undergo a dramatic structural change in order to be internalized into the cytosol, where it finally performs its function. The molecular mechanism of toxin transit across the membrane is not well known, but the available experimental evidence indicates that one of the three domains of the toxin, called the central α-helical domain, inserts into the lipid bilayer, so favoring the translocation of the catalytic domain. This process is driven by the acidic pH of the endosomal lumen. Here, we describe the crystal structure of DT grown at acidic pH in the presence of bicelles. We were unable to freeze the moment of DT insertion into the lipid bilayer, but our crystal structure indicates that the low pH causes the unfolding of the TH2, TH3 and TH4 α-helices. This event gives rise to the exposure of a hydrophobic surface that includes the TH5 and TH8 α-helices, and the loop region connecting the TH8 and TH9 α-helices. Their exposure is probably favored by the presence of lipid bilayers in the crystallization solution, and they appear to be ready to insert into the membrane.

PubMed: 24628974
DOI: 10.1111/febs.12783

実験手法

X-RAY DIFFRACTION (2.8 Å)