Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism

Abstract

(2013) 'Molecular assembly of the aerolysin pore reveals a swirling membrane-insertion mechanism.', Nature chemical biology., 9 (10). pp. 623-629. Further information on publisher's website:https://doi.org/10.1038/nchembio.1312Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractAerolysin is the founding member of a super-family of ß-pore forming toxins for which the pore structure is unknown. We have combined X-ray crystallography, cryo-electron microscopy (EM), molecular dynamics and computational modeling to determine the structures of aerolysin mutants in their monomeric and heptameric forms, trapped at various stages of the pore formation process. A dynamic modeling approach based on swarm intelligence was applied whereby the intrinsic flexibility of aerolysin extracted from new X-ray structures was utilized to fully exploit the cryo-EM spatial restraints. Using this integrated strategy, we obtained a radically new arrangement of the prepore conformation and a near-atomistic structure of the aerolysin pore, which is fully consistent with all biochemical data available so far. Upon transition from the prepore to pore, the aerolysin heptamer shows a unique concerted swirling movement, accompanied by a vertical collapse of the complex, ultimately leading to the insertion of a transmembrane ß-barrel.3

Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins

“…Moreover, based on the results of biochemical analysis, Sato et al 34 recently showed that the transmembrane b-hairpin of perfringolysin O, a bacterial cholesterol-dependent cytolysin, was unfolded and had freedom of motion in the prepore state, which agreed with the present structural data, although the molecular architecture of perfringolysin O is entirely different from those of staphylococcal b-PFTs. On the other hand, the pore formation mechanism recently proposed for aerolysin based on the cryo-electron miccroscopy structures-a swirling membrane insertion mechanism-is fundamentally different 35 . There should be diversity in the mode of action although the b-barrel architecture is commonly used as a transmembrane pore.…”

Detection of Single Oligonucleotide by an Aerolysin Nanopore

“…随后, Aerolysin 被应用于蛋白的 折叠和去折叠动力学过程 [13] 、聚乙二醇分子与孔的作 用 [14] 、低聚糖的聚集程度 [15] 和酶降解的动力学 [16] 等研 The statistical analysis events were acquired from three independent nanopore experiments and the number of current blockages in each experiment is 8000 at least 此, Aerolysin 纳米孔道在寡聚核苷酸检测方面表现出更 高的空间分辨能力. 根据最新的 Aerolysin 结构研究报 道, Aerolysin 跨膜蛋白的孔径约为 1.0 nm [17] , 这一独特 的几何结构可能是 Aerolysin 纳米孔道在寡聚核苷酸检 测表现出更高空间分辨率的原因. 纳米孔道检测方法参照我们之前的研究结果 [19] .…”

The membrane attack complex, perforin and cholesterol-dependent cytolysin superfamily of pore-forming proteins

“…Depending on the secondary structure elements that form the transmembrane pores, PFPs are broadly classified as α-PFPs, which utilise amphipathic α-helices for pore formation (e.g. Cry toxins produced by Bacillus thuringiensis (Ounjai et al, 2007;Pardo-López et al, 2013), diphtheria toxin (Leka et al, 2014;Ghatak et al, 2015) and colicin produced by Escherichia coli (Cascales et al, 2007;Housden and Kleanthous, 2012); or as β-PFPs with pores built of amphipathic β-hairpins organised into a transmembrane β-barrel (for example, anthrax protective antigen (Collier, 2009;Jiang et al, 2015), aerolysin toxin produced by Aeromonas hydrophila (Degiacomi et al, 2013) and α-hemolysin of Staphylococcus aureus (Menestrina et al, 2003;Sugawara et al, 2015). Many PFPs are bacterial toxins and are able to damage host membranes to gain access to cells or cell contents, or to kill cells.…”