<br>结合诱导的脂质结构域：肽膜与 PIP2 和 PS 的相互作用,Biophysical Journal

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结合诱导的脂质结构域：肽膜与 PIP2 和 PS 的相互作用
Biophysical Journal ( IF 3.2 ) Pub Date : 2023-12-23 , DOI: 10.1016/j.bpj.2023.12.019
Ziareena A Al-Mualem ₁ , Xiaobing Chen ₁ , Azam Shafieenezhad ₂ , Eric N Senning ₂ , Carlos R Baiz ₁

Affiliation

细胞信号转导是一个重要的过程，涉及脂质和蛋白质之间复杂的相互作用。肉豆蔻酰化的富含丙氨酸的 C 激酶底物（MARCKS）已被确立为一种关键的信号调节因子，具有一系列生物学作用。其效应结构域（ED）将蛋白质锚定在质膜上，在含有磷脂酰肌醇 4,5-二磷酸（PIP2）和磷脂酰丝氨酸（PS）的膜中诱导结构域形成。控制 MARCKS-ED 与膜结合的机制仍然难以捉摸。在这里，我们使用二维红外光谱和荧光各向异性研究了组成依赖性的亲和力和 MARCKS-ED 结合诱导的界面环境中的变化。两种带负电荷的脂质都促进 MARCKS-ED 与脂质囊泡的结合。尽管脂质-水界面处的氢键结构在具有不同脂质组成的囊泡之间保持相似性，但由于脂质和肽之间的特定相互作用，界面水的动力学显示出不同的模式。我们的研究结果还显示，PIP2 被结合的肽隔离，而 PS 的分布在肽结合时没有表现出明显的变化。有趣的是，PIP2 和 PS 在存在和不存在 MARCKS-ED 的情况下都共定位到结构域中。更广泛地说，这项工作提供了关于膜组成对结合影响的分子见解。

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Binding-induced lipid domains: Peptide-membrane interactions with PIP2 and PS

Cell signaling is an important process involving complex interactions between lipids and proteins. The myristoylated alanine-rich C-kinase substrate (MARCKS) has been established as a key signaling regulator, serving a range of biological roles. Its effector domain (ED), which anchors the protein to the plasma membrane, induces domain formation in membranes containing phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS). The mechanisms governing the MARCKS-ED binding to membranes remain elusive. Here, we investigate the composition-dependent affinity and MARCKS-ED-binding-induced changes in interfacial environments using two-dimensional infrared spectroscopy and fluorescence anisotropy. Both negatively charged lipids facilitate the MARCKS-ED binding to lipid vesicles. Although the hydrogen-bonding structure at the lipid-water interface remains comparable across vesicles with varied lipid compositions, the dynamics of interfacial water show divergent patterns due to specific interactions between lipids and peptides. Our findings also reveal that PIP2 becomes sequestered by bound peptides, while the distribution of PS exhibits no discernible change upon peptide binding. Interestingly, PIP2 and PS become colocalized into domains both in the presence and absence of MARCKS-ED. More broadly, this work offers molecular insights into the effects of membrane composition on binding.

更新日期：2023-12-23

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