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近原生拉伸敏感膜微域的冷冻电镜结构获解析
作者:小柯机器人 发布时间:2024/7/28 22:04:16

瑞士日内瓦大学Robbie Loewith研究小组揭示了近原生拉伸敏感膜微域的冷冻电镜结构。相关论文于2024年7月24日在线发表于国际学术期刊《自然》。

研究人员分离出了近原生的eisosome,形成由Pil1/Lsp1与质膜脂质结合的螺旋管,并通过螺旋重构解析了其结构。结构显示出膜脂质的惊人组织,并使用体外重构和分子动力学模拟,确认了被Pil1/Lsp1覆盖物隔离的PI(4,5)P2、磷脂酰丝氨酸和固醇分子的定位。对原生来源的eisosome进行三维可变性分析显示了Pil1/Lsp1晶格的动态拉伸,这种拉伸影响了这些脂质的隔离。

总体而言,这些结果支持这样一种机制:Pil1/Lsp1晶格的拉伸释放了原本被Pil1/Lsp1覆盖物锚定的脂质,从而提供了eisosome BAR结构域蛋白如何创建机械敏感膜微域的机械洞察。

研究人员表示,生物膜被划分为功能区域,称为膜微域,这些区域含有特定的脂质和蛋白质。由于只有少数技术可以在不破坏脂质原生行为的情况下对其进行可视化,因此膜微域的组成和组织仍然存在争议。酵母的eisosome由BAR结构域蛋白Pil1和Lsp1组成,支撑着一个膜隔室,通过展平和释放被隔离的因子来感应和响应机械应力。

附:英文原文

Title: Cryo-EM architecture of a near-native stretch-sensitive membrane microdomain

Author: Kefauver, Jennifer M., Hakala, Markku, Zou, Luoming, Alba, Josephine, Espadas, Javier, Tettamanti, Maria G., Gaji, Jelena, Gabus, Caroline, Campomanes, Pablo, Estrozi, Leandro F., Sen, Nesli E., Vanni, Stefano, Roux, Aurlien, Desfosses, Ambroise, Loewith, Robbie

Issue&Volume: 2024-07-24

Abstract: Biological membranes are partitioned into functional zones termed membrane microdomains, which contain specific lipids and proteins1,2,3. The composition and organization of membrane microdomains remain controversial because few techniques are available that allow the visualization of lipids in situ without disrupting their native behaviour3,4. The yeast eisosome, composed of the BAR-domain proteins Pil1 and Lsp1 (hereafter, Pil1/Lsp1), scaffolds a membrane compartment that senses and responds to mechanical stress by flattening and releasing sequestered factors5,6,7,8,9. Here we isolated near-native eisosomes as helical tubules made up of a lattice of Pil1/Lsp1 bound to plasma membrane lipids, and solved their structures by helical reconstruction. Our structures reveal a striking organization of membrane lipids, and, using in vitro reconstitutions and molecular dynamics simulations, we confirmed the positioning of individual PI(4,5)P2, phosphatidylserine and sterol molecules sequestered beneath the Pil1/Lsp1 coat. Three-dimensional variability analysis of the native-source eisosomes revealed a dynamic stretching of the Pil1/Lsp1 lattice that affects the sequestration of these lipids. Collectively, our results support a mechanism in which stretching of the Pil1/Lsp1 lattice liberates lipids that would otherwise be anchored by the Pil1/Lsp1 coat, and thus provide mechanistic insight into how eisosome BAR-domain proteins create a mechanosensitive membrane microdomain.

DOI: 10.1038/s41586-024-07720-6

Source: https://www.nature.com/articles/s41586-024-07720-6

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html