Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix.
Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix.
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粗粒度模拟表明Epsin n -末端同源结构域可以在没有末端两亲螺旋的情况下感知膜曲率。
DOI：
10.1021/acsnano.0c05960
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发表时间：
2020-12-22
期刊：
影响因子：
17.1
通讯作者：
Stevens MM
中科院分区：
文献类型：
--
作者：
Belessiotis-Richards A;Higgins SG;Sansom MSP;Alexander-Katz A;Stevens MM
在细胞生物学中，纳米尺度的膜曲率是细胞吞噬、胞吐和细胞迁移等功能所必需的一种常见特征。这些过程需要细胞骨架在膜上施加力，使其变形。胞浆蛋白含有与膜结合的特定基序，将膜连接到内部细胞骨架机械。这些基序经常与存在于细胞膜上的带电磷脂酰肌醇磷脂结合，这些磷脂在信号转导中发挥重要作用。这些脂类对膜的变形过程是重要的，例如内吞作用，但关于它们在通过蛋白质结构域感知膜纳米曲率中的作用仍不清楚。利用粗粒分子动力学模拟，我们研究了一个模型曲率活性蛋白结构域--epsin N-末端同源结构域(Ten)与弯曲的脂膜的相互作用。膜内阴离子脂类(磷脂酰肌醇4，5-二磷酸和磷脂酰丝氨酸)的结合、蛋白质骨架的灵活性和结构域内的结构变化被发现影响结构域在弯曲的膜区以纳米级的精度识别、结合和定位的能力。这些发现表明，第10结构域可以在没有末端两亲性α螺旋存在的情况下通过另一个结构区域(我们称之为H3)来感知膜曲率，再次强调了纳米膜曲率与蛋白质功能之间的关键关系。
Nanoscale membrane curvature is a common feature in cell biology required for functions such as endocytosis, exocytosis and cell migration. These processes require the cytoskeleton to exert forces on the membrane to deform it. Cytosolic proteins contain specific motifs which bind to the membrane, connecting it to the internal cytoskeletal machinery. These motifs often bind charged phosphatidylinositol phosphate lipids present in the cell membrane which play significant roles in signaling. These lipids are important for membrane deforming processes, such as endocytosis, but much remains unknown about their role in the sensing of membrane nanocurvature by protein domains. Using coarse-grained molecular dynamics simulations, we investigated the interaction of a model curvature active protein domain, the epsin N-terminal homology domain (ENTH), with curved lipid membranes. The combination of anionic lipids (phosphatidylinositol 4,5-bisphosphate and phosphatidylserine) within the membrane, protein backbone flexibility, and structural changes within the domain were found to affect the domain’s ability to sense, bind, and localize with nanoscale precision at curved membrane regions. The findings suggest that the ENTH domain can sense membrane curvature without the presence of its terminal amphipathic α helix via another structural region we have denoted as H3, re-emphasizing the critical relationship between nanoscale membrane curvature and protein function.
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DOI：
10.1083/jcb.201608071
发表时间：
2017-01-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kadlecova Z;Spielman SJ;Loerke D;Mohanakrishnan A;Reed DK;Schmid SL
通讯作者：
Schmid SL
DOI：
10.1007/s00232-014-9733-1
发表时间：
2015-06
期刊：
The Journal of membrane biology
影响因子：
--
作者：
Perrin BS Jr;Sodt AJ;Cotten ML;Pastor RW
通讯作者：
Pastor RW
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
基于磷脂酰肌醇 4,5-二磷酸重新分布的传感机制启动吞噬程序
影响因子：
16.6
作者：
Mu L;Tu Z;Miao L;Ruan H;Kang N;Hei Y;Chen J;Wei W;Gong F;Wang B;Du Y;Ma G;Amerein MW;Xia T;Shi Y
通讯作者：
Shi Y
影响因子：
3.3
作者：
Antonescu CN;Aguet F;Danuser G;Schmid SL
通讯作者：
Schmid SL