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Effects on Membrane Lateral Pressure Suggest Permeation Mechanisms for Bacterial Quorum Signaling Molecules

机译:对膜侧向压力的影响提示细菌群体信号分子的渗透机制

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Quorum sensing is an intricate example of “social” behavior in microbial communities mediated by small secreted molecules (autoinducers). The mechanisms of membrane permeation remain elusive for many of them. Here we present the assessment of membrane permeability for three natural autoinducers and four synthetic analogues based on their polarity, surface activity, affinity for lipid monolayers, and ability to induce lateral pressure changes in the inner E. coli membrane sensed by the bacterial tension-activated channel MscS. AI-1 (N-(3-oxodecanoyl)-l-homoserine lactone) is surface-active, and it robustly inserts into lipid monolayers, indicating strong propensity toward membranes. When presented to membrane patches from the cytoplasmic side, AI-1 transiently shifts MscS’s activation curve toward higher tensions due to intercalation into the cytoplasmic leaflet followed by redistribution to the opposite side. Indole showed no detectable surface activity at the air–water interface but produced a moderate increase of lateral pressure in monolayers and was potent at shifting activation curves of MscS, demonstrating transients on sequential additions. AI-2 (4,5-dihydroxy-2,3-pentanedione, DPD) showed little activity at the interfaces, correspondingly with no effect on MscS activation. After chemical modification with isobutyl, hexyl, or heptyl chains, AI-2 displayed strong surface activity. Hexyl and especially heptyl AI-2 induced robust transient shifts of MscS activation curves. The data strongly suggest that both AI-1 and indole are directly permeable through the membrane. AI-2, more hydrophilic, shows low affinity toward lipids and thus requires a transport system, whereas alkyl analogues of AI-2 should permeate the membrane directly.
机译:群体感应是由分泌小分子(自动诱导剂)介导的微生物群落“社会”行为的复杂例子。膜渗透的机制对许多人来说仍然难以捉摸。在这里,我们根据其极性,表面活性,对脂质单分子膜的亲和力以及诱导细菌张力激活感测的内部大肠杆菌膜的侧向压力变化的能力,对三种天然自诱导剂和四种合成类似物的膜渗透性进行了评估。频道MscS。 AI-1(N-(3-氧十二烷酰基)-1-高丝氨酸内酯)具有表面活性,可牢固地插入脂质单层,表明对膜具有很强的倾向。当从细胞质的一面呈现在膜片上时,AI-1会由于插入到细胞质的小叶中并随后重新分布到另一面而使MscS的激活曲线暂时向更高的张力移动。吲哚在空气-水界面处没有可检测到的表面活性,但在单层中产生了适度的侧向压力增加,并且在移动MscS的活化曲线上很有效,证明了连续添加时的瞬变。 AI-2(4,5-二羟基-2,3-戊二酮,DPD)在界面处几乎没有活性,因此对MscS活化没有影响。用异丁基,己基或庚基链进行化学修饰后,AI-2显示出很强的表面活性。己基,尤其是庚基AI-2诱导了MscS激活曲线的强劲瞬态位移。数据强烈表明AI-1和吲哚均可直接透过膜渗透。 AI-2更亲水,对脂质的亲和力低,因此需要转运系统,而AI-2的烷基类似物应直接渗透膜。

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