Spatial arrangement of proteins in planar and curved membranes by PPM 3.0
Spatial arrangement of proteins in planar and curved membranes by PPM 3.0
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DOI：
10.1002/pro.4219
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发表时间：
2021-11-08
期刊：
影响因子：
8
通讯作者：
Pogozheva, Irina D.
中科院分区：
文献类型：
--
作者：
Lomize, Andrei L.;Todd, Spencer C.;Pogozheva, Irina D.
细胞突起、内陷和许多细胞内细胞器具有强烈弯曲的膜区域。诱导、感知或稳定这些区域的跨膜和外周膜蛋白不能正确地装配到单个平坦的双层中。为了处理这些蛋白质，我们开发了一种新的方法和网络工具PPM 3.0，用于将蛋白质定位在弯曲或平面，单个或多个膜中。该方法通过将膜变形蛋白质结构布置在单个或几个球形或平面膜部分中来确定膜变形蛋白质结构的能量最佳空间位置、疏水厚度和固有曲率半径。此外，它可以定义同时跨越几个膜的蛋白质的脂质嵌入区域，或确定肽在球形胶束中的最佳位置。PPM 3.0网络服务器使用17种生物膜和4种人工双层。它是公开的。PPM 3.0应用于识别和表征128种具有显著内在曲率的蛋白质在膜中的排列，例如BAR结构域、膜联蛋白、压电和MscS机械敏感通道、阳离子-氯共转运蛋白以及线粒体ATP酶、钙单向转运蛋白和TOM复合物。这些蛋白质形成主要位于线粒体、质膜和内体中的大复合物。细菌药物外排泵AcrAB-TolC、MexAB-OrpM和MacAB-TolC的结构位于细菌细胞膜的两个膜中，而多聚体间隙连接通道的结构则排列在两个相对的细胞膜中。
Cellular protrusions, invaginations, and many intracellular organelles have strongly curved membrane regions. Transmembrane and peripheral membrane proteins that induce, sense, or stabilize such regions cannot be properly fitted into a single flat bilayer. To treat such proteins, we developed a new method and a web tool, PPM 3.0, for positioning proteins in curved or planar, single or multiple membranes. This method determines the energetically optimal spatial position, the hydrophobic thickness, and the radius of intrinsic curvature of a membrane-deforming protein structure by arranging it in a single or several sphere-shaped or planar membrane sections. In addition, it can define the lipid-embedded regions of a protein that simultaneously spans several membranes or determine the optimal position of a peptide in a spherical micelle. The PPM 3.0 web server operates with 17 types of biological membranes and 4 types of artificial bilayers. It is publicly available at . PPM 3.0 was applied to identify and characterize arrangements in membranes of 128 proteins with a significant intrinsic curvature, such as BAR domains, annexins, Piezo, and MscS mechanosensitive channels, cation-chloride cotransporters, as well as mitochondrial ATP synthases, calcium uniporters, and TOM complexes. These proteins form large complexes that are mainly localized in mitochondria, plasma membranes, and endosomes. Structures of bacterial drug efflux pumps, AcrAB-TolC, MexAB-OrpM, and MacAB-TolC, were positioned in both membranes of the bacterial cell envelop, while structures of multimeric gap-junction channels were arranged in two opposed cellular membranes.