4EE2

Crystal Structure of Anthrax Protective Antigen K446M Mutant to 1.91-A Resolution

4EE2 の概要

• エントリーDOI: 10.2210/pdb4ee2/pdb
• 関連するPDBエントリー: 1ACC 1TZO 3HVD 3TEW 3TEX
• 分子名称: Protective antigen, CALCIUM ION (3 entities in total)
• 機能のキーワード: anthrax toxin, cell-binding, assembly, channel formation, protein translocation, toxin, transport protein
• 由来する生物種: Bacillus anthracis (anthrax,anthrax bacterium)
• 細胞内の位置: Secreted, extracellular space: P13423
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 82982.19

構造登録者

Kintzer, A.F.,Krantz, B.A. (登録日: 2012-03-28, 公開日: 2012-10-24, 最終更新日: 2023-09-13)

主引用文献

Kintzer, A.F.,Tang, I.I.,Schawel, A.K.,Brown, M.J.,Krantz, B.A.
Anthrax toxin protective antigen integrates poly-gamma-D-glutamate and pH signals to sense the optimal environment for channel formation.
Proc.Natl.Acad.Sci.USA, 109:18378-18383, 2012

PubMed Abstract: Many toxins assemble into oligomers on the surface of cells. Local chemical cues signal and trigger critical rearrangements of the oligomer, inducing the formation of a membrane-fused or channel state. Bacillus anthracis secretes two virulence factors: a tripartite toxin and a poly-γ-d-glutamic acid capsule (γ-DPGA). The toxin's channel-forming component, protective antigen (PA), oligomerizes to create a prechannel that forms toxic complexes upon binding the two other enzyme components, lethal factor (LF) and edema factor (EF). Following endocytosis into host cells, acidic pH signals the prechannel to form the channel state, which translocates LF and EF into the host cytosol. We report γ-DPGA binds to PA, LF, and EF, exhibiting nanomolar avidity for the PA prechannel oligomer. We show PA channel formation requires the pH-dependent disruption of the intra-PA domain-2-domain-4 (D2-D4) interface. γ-DPGA stabilizes the D2-D4 interface, preventing channel formation both in model membranes and cultured mammalian cells. A 1.9-Å resolution X-ray crystal structure of a D2-D4-interface mutant and corresponding functional studies reveal how stability at the intra-PA interface governs channel formation. We also pinpoint the kinetic pH trigger for channel formation to a residue within PA's membrane-insertion loop at the inter-PA D2-D4 interface. Thus, γ-DPGA may function as a chemical cue, signaling that the local environment is appropriate for toxin assembly but inappropriate for channel formation.

PubMed: 23100533
DOI: 10.1073/pnas.1208280109

実験手法

X-RAY DIFFRACTION (1.91 Å)