3J9C

CryoEM single particle reconstruction of anthrax toxin protective antigen pore at 2.9 Angstrom resolution

3J9C の概要

• エントリーDOI: 10.2210/pdb3j9c/pdb
• EMDBエントリー: 6224 6225
• 分子名称: Protective antigen PA-63, CALCIUM ION (2 entities in total)
• 機能のキーワード: bacterial toxin, anthrax toxin, protective antigen, protein translocation channel, toxin, transport protein
• 由来する生物種: Bacillus anthracis (anthrax)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 63099.17

構造登録者

Jiang, J.,Pentelute, B.L.,Collier, R.J.,Zhou, Z.H. (登録日: 2014-12-25, 公開日: 2015-03-11, 最終更新日: 2024-02-21)

主引用文献

Jiang, J.,Pentelute, B.L.,Collier, R.J.,Zhou, Z.H.
Atomic structure of anthrax protective antigen pore elucidates toxin translocation.
Nature, 521:545-549, 2015

PubMed Abstract: Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. Protective antigen is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. On the basis of biochemical and electrophysiological results, researchers have proposed that a phi (Φ)-clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses protein translocation via a charge-state-dependent Brownian ratchet. Although atomic structures of protective antigen prepores are available, how protective antigen senses low pH, converts to active pore, and translocates lethal factor and oedema factor are not well defined without an atomic model of its pore. Here, by cryo-electron microscopy with direct electron counting, we determine the protective antigen pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic Φ-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low pH is sensed and the membrane-spanning channel is formed.

PubMed: 25778700
DOI: 10.1038/nature14247

実験手法

ELECTRON MICROSCOPY (2.9 Å)