通过SNARE复合体的定向和完整组装进行膜融合中间体
Javier M Hernandez1, Alexander Stein, Elmar Behrmann
1Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
概括
可溶性N-乙基胺胺敏感因子附着蛋白受体 (SNAREs) 驱动膜融合. SNARE组件紧密地对接双层,但完全的融合需要额外的SNARE复合组件,启动脂质应力以形成孔隙.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 膜生物物理学 膜生物物理学
背景情况:
- 细胞膜融合是一种基本的生物过程,涉及脂质双层的融合.
- 可溶性N-乙基胺胺敏感因子附着蛋白受体 (SNAREs) 形成一个四螺旋束介导膜融合.
- 目前尚不清楚SNARE复杂组件驱动核聚变中间体的确切机制.
研究的目的:
- 研究SNARE复合组件在产生膜聚变中间体中的作用.
- 在融合过程中识别和描述SNARE的结构状态.
- 阐明从SNARE复合体组装到双层融合的事件序列.
主要方法:
- 利用无细胞系统重组膜融合.
- 用人使用的中间材料的视觉识别.
- 在融合前阶段停止了SNARE聚变机器.
主要成果:
- 在膜融合途径中确定了不同的中间体.
- 证明了部分和定向的SNARE组装导致紧密的双层对接.
- 证明高效的聚变和扩展的半聚变需要SNARE组件超出核心复合体,参与膜连接连接器.
- 建议在延伸的对接区边缘的脂质应力启动融合.
结论:
- 复杂的SNARE组装是一个阶段性过程,对于膜融合至关重要.
- 通过部分SNARE组装实现紧密的双层对接.
- 完全融合需要广泛的SNARE复合组装,并诱导脂质应力.
- 这项研究为SNARE介导的膜融合启动提供了机理性的洞察力.
相关概念视频
SNAREs and Membrane Fusion
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...
Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
Mechanism of Filopodia Formation
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Mechanisms of Membrane Domain Formation
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...


