How Interaction of Perfringolysin O with Membranes Is Controlled by Sterol Structure, Lipid Structure, and Physiological Low pH
How Interaction of Perfringolysin O with Membranes Is Controlled by Sterol Structure, Lipid Structure, and Physiological Low pH
复制标题
甾醇结构、脂质结构和生理低 pH 值如何控制 Perfringolysin O 与膜的相互作用
DOI：
--
复制
发表时间：
2008
影响因子：
4.8
通讯作者：
E. London
中科院分区：
文献类型：
--
作者：
L. D. Nelson;A. Johnson;E. London
产气荚膜梭菌溶素O（PFO）是一种固醇依赖性的、成孔的细胞溶素。为了了解PFO膜相互作用的分子基础，我们研究了它对甾醇和脂质结构以及水环境的依赖性。PFO与多种固醇相互作用，尽管结合受到固醇环中双键位置、固醇侧链结构和固醇极性基团结构的影响。重要的是，促进有序膜结构域（脂筏）形成的甾醇结构对于相互作用并不重要。PFO膜相互作用也受到磷脂酰基链结构的影响，与胆固醇的紧密酰基链包装呈负相关。使用前孔Y181 A突变体的实验表明，甾醇结合强度和特异性不受PFO是否形成跨膜β-桶的影响。结合起来，这些观察结果是一致的模型，其中的强度和特异性的甾醇相互作用产生的甾醇与结构域4和膜内的甾醇化学活性的相互作用。与PFO结合的固醇的脂筏结合部分可以保持大部分暴露于脂质双层。这些结果对PFO筏亲和力的起源产生了重要的限制。另外的实验表明，在低pH和中性pH下膜插入的PFO的结构是相似的，如通过磷脂和甾醇结构对PFO性质和膜相互作用的影响所判断的。然而，低pH值增强PFO膜结合，寡聚化和孔形成。在脂质囊泡模仿exofacial（外）膜小叶，全氟辛烷磺酸膜结合最大的pH值为5.5-6。这与PFO功能涉及酸性空泡的假设一致。
Perfringolysin O (PFO) is a sterol-dependent, pore-forming cytolysin. To understand the molecular basis of PFO membrane interaction, we studied its dependence upon sterol and lipid structure and aqueous environment. PFO interacted with diverse sterols, although binding was affected by double bond location in the sterol rings, sterol side chain structure, and sterol polar group structure. Importantly, a sterol structure promoting formation of ordered membrane domains (lipid rafts) was not critical for interaction. PFO membrane interaction was also affected by phospholipid acyl chain structure, being inversely related to tight acyl chain packing with cholesterol. Experiments using the pre-pore Y181A mutant demonstrated that sterol binding strength and specificity was not affected by whether PFO forms a transmembrane β-barrel. Combined, these observations are consistent with a model in which the strength and specificity of sterol interaction arises from both sterol interactions with domain 4 and sterol chemical activity within membranes. The lipid raft-binding portions of sterol bound to PFO may remain largely exposed to the lipid bilayer. These results place important constraints upon the origin of PFO raft affinity. Additional experiments demonstrated that the structure of membrane-inserted PFO at low and neutral pH was similar as judged by the effect of phospholipid and sterol structure upon PFO properties and membrane interaction. However, low pH enhanced PFO membrane binding, oligomerization, and pore formation. In lipid vesicles mimicking the exofacial (outer) membrane leaflet, PFO-membrane binding was maximal at pH 5.5–6. This is consistent with the hypothesis that PFO function involves acidic vacuoles.
登录
查看更多内容
插入膜的白喉毒素 T 结构域的亲水螺旋的形貌：TH1-TH3 作为亲水系链。
影响因子：
2.9
作者：
Wang,Jie;Rosconi,MichaelP;London,Erwin
通讯作者：
London,Erwin
白喉毒素在高温下的构象与透膜低pH状态下的构象相似。
DOI：
10.1073/pnas.83.7.2002
发表时间：
1986
影响因子：
11.1
作者：
Zhao,JM;London,E
通讯作者：
London,E
影响因子：
3.4
作者：
F. Nicol;S. Nir;F. Szoka
通讯作者：
F. Nicol;S. Nir;F. Szoka
影响因子：
--
作者：
Nir, S;Nicol, F;Szoka, FC
通讯作者：
Szoka, FC
DOI：
10.1073/pnas.0403229101
发表时间：
2005-01-18
影响因子：
11.1
作者：
Polekhina, G;Giddings, KS;Parker, MW
通讯作者：
Parker, MW