合成素1A跨膜域棕化诱导了一个融合性构造
Dong An1, Satyan Sharma2, Manfred Lindau1
1Department of Physiology and Biophysics, University of Miami Miller School, Miami, Florida.
Biophysical journal
|May 24, 2025
概括
合成素1A (Stx1A) 跨膜域的棕化有助于SNARE复合体的形成和自发的神经递质释放. 然而,它也延迟了融合孔的开放,并改变了膜融合事件期间的动态.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 神经递质释放依赖于通过SNARE蛋白质调解的突触囊泡融合.
- 在C271/C272的Syntaxin 1A (Stx1A) 棕化与自发的神经递质释放有关.
- 在膜融合中SNARE跨膜域 (TMD) 棕化作用尚未完全理解.
研究的目的:
- 调查SNARE TMD棕化对膜融合的结构和功能影响.
- 阐明 Stx1A 棕化影响神经递质释放的机制.
主要方法:
- 使用MARTINI力场进行粗粒度分子动力学模拟.
- 对单个SNARE蛋白,t-SNARE复合体和融合孔形成的模拟.
主要成果:
- Stx1A棕化稳定了直立的SNARE域形状,促进了早期的SNARE复合体形成.
- Stx1A TMD 棕化延迟了融合孔的开放,并减少了闪开放时间.
- Synaptobrevin 2 (Syb2) 棕化并没有显著影响融合孔动态.
结论:
- Stx1A TMD棕化起着双重作用,促进早期SNARE复合体的形成,并影响后来的融合孔动态.
- 在神经递质释放的多个阶段中,SNARE TMD 棕化是至关重要的.
- 这些发现为SNARE介导的膜融合提供了机械的见解.
更多相关视频
相关概念视频
SNAREs and Membrane Fusion
12.4K
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...
12.4K
Fusion of Secretory Vesicles with the Plasma Membrane
16.6K
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...
16.6K
Translocation of Proteins into the Mitochondria
12.4K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
12.4K
Insertion of Single-pass Transmembrane Proteins in the RER
16.8K
Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
16.8K
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
Mechanism of Filopodia Formation
3.1K
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...
3.1K


