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Ca~(2+)–dimethylphosphate complex formation: Providing insight into Ca~(2+)-mediated local dehydration and membrane fusion in cells

机译:Ca〜(2 +)–磷酸二甲酯复合物的形成:洞悉Ca〜(2+)介导的局部脱水和细胞膜融合

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摘要

Earlier studies using X-ray diffraction, light scattering, photon correlation spectroscopy, and atomic force microscopy, strongly suggest that SNARE-induced membrane fusion in cells proceeds as a result of calcium bridging opposing bilayers. The bridging of phospholipid heads groups in the opposing bilayers by calcium leads to the release of water from hydrated Ca2+ ions as well as the loosely coordinated water at PO-lipid head groups. Local dehydration of phospholipid head groups and the calcium, bridging opposing bilayers, then leads to destabilization of the lipid bilayers and membrane fusion. This hypothesis was tested in the current study by atomistic molecular dynamic simulations in the isobaric–isothermal ensemble using hydrated dimethylphosphate anions (DMP?) and calcium cations. Results from the study demonstrate, formation of DMP–Ca2+ complexes and the consequent removal of water, supporting the hypothesis. Our study further demonstrates that as a result of Ca2+–DMP self-assembly, the distance between anionic oxygens between the two DMP molecules is reduced to 2.92 ?, which is in close agreement with the 2.8 ? SNARE-induced apposition established between opposing bilayers, reported earlier from X-ray diffraction measurements.
机译:早期使用X射线衍射,光散射,光子相关光谱和原子力显微镜的研究强烈表明,网罗SNARE诱导的细胞膜融合是钙桥接双层的结果。钙在相对的双层中桥接磷脂头基团导致水合的Ca2 +离子释放水,以及PO-脂质头基团上的配位松散的水。磷脂头基和钙的局部脱水,桥接相对的双层,然后导致脂质双层的不稳定和膜融合。在当前的研究中,通过使用水合磷酸二甲酯磷酸根阴离子(DMP?)和钙阳离子在等压-等温整体中进行原子分子动力学模拟,验证了该假设。研究结果表明,DMP–Ca2 +复合物的形成以及随后的除水作用均支持了这一假说。我们的研究进一步表明,由于Ca2 + –DMP自组装的结果,两个DMP分子之间的阴离子氧之间的距离减少到2.92Ω,与2.8Ω·D紧密一致。 SNARE诱导的对立双层之间的并置,早些时候由X射线衍射测量报告。

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