通过SNX1-SNX5进行货物和膜识别的劳动分工:来自多尺度建模的见解
Satya Chaithanya Duggisetty1, Gaurav Kumar1, Krishnakanth Baratam2
1Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka, India.
Biophysical journal
|November 9, 2025
概括
排序nexin (SNXs) 是细胞贩运的关键蛋白质. 这项研究揭示了SNX1-SNX5异构体如何结合膜,并使用先进的模拟,独立于逆转分子复合体识别货物.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 计算生物学 计算生物学
背景情况:
- 排序nexins (SNXs) 对于膜重塑和货物分类至关重要.
- SNX 蛋白利用 BAR 和 phox 同源 (PX) 域进行器官结合和膜相互作用.
- 这种SNX1-SNX5异构体参与了不依赖于复原体的货物分类和膜重塑路径.
研究的目的:
- 阐明SNX1-SNX5异构体的有机细胞膜特异性和逆转激素独立的载荷识别的分子机制.
- 通过计算模拟,研究PX域在SNX1-SNX5函数中的作用.
主要方法:
- 在脂质双层上对孤立的PXD和全长的SNX1-SNX5进行全原子分子动力学模拟.
- 模拟衍生的结合姿势与冷EM结构的比较.
- 在SNX5-PXD和CI-MPR货物之间蛋白质与蛋白质相互作用的元动力学模拟.
- 用动态三角化表面和连续力学来模拟新出现的行为.
主要成果:
- SNX1-PXD表现出强大的膜结合,独立于表面基本残留物.
- 模拟姿势提供了对隔离PXD与膜的关联的见解.
- π-π相互作用介于SNX5-PXD和CI-MPR之间的结合,SNX5.5的结合自由能量是有利的.
- 中视镜模拟模型货物封存和内体管通过SNX1-SNX5.5形成.
结论:
- SNX1-SNX5异构体具有特定的膜结合和货物识别的内在机制.
- 计算方法揭示了SNX1-SNX5在膜贩运中的关键相互作用和新兴特性.
- 这些发现有助于理解细胞运输中的逆转激素独立路径.
相关概念视频
SNAREs and Membrane Fusion
12.3K
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
12.3K
Clathrin Coated Vesicles
9.0K
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
9.0K
Pinching-off of Coated Vesicles
4.0K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
4.0K
Transport Across the Golgi
5.8K
While it is unclear how molecules move between adjacent Golgi cisternae, it is apparent that the molecules move from cis- cisterna, the entry face, to the trans- cisterna, the exit face. Experiments initially suggested vesicles that bud from one cisterna and fuse with the next cisterna to transport proteins between the cisternae. This vesicular transport model describes the Golgi apparatus as a relatively static structure with a unique enzyme composition in each cisterna. Molecules are...
5.8K
Introduction to Membrane Traffic
9.2K
The ER, Golgi apparatus, endosomes, and lysosomes work in tandem to modify, sort, and package proteins and lipids. An integrated membrane trafficking network facilitates the back and forth shuttling of molecules within different organelles in the same cell or across the cell membrane.
The transport of soluble and membrane proteins is mediated by transport vesicles that collect cargo from one cellular compartment and deliver it to another by fusing with the target organelle membrane. The Rab...
The transport of soluble and membrane proteins is mediated by transport vesicles that collect cargo from one cellular compartment and deliver it to another by fusing with the target organelle membrane. The Rab...
9.2K
Coat Assembly and GTPases
4.2K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
4.2K


