在Sec18 ATP水解中,Sec17从跨-SNARE复合体中选择性释放出来,抑制了膜融合
Karina Lopes1, Amy Orr1, William Wickner1
1Department of Biochemistry and Cell Biology Geisel School of Medicine at Dartmouth 7200 Vail uilding Hanover, NH 03755.
Molecular biology of the cell
|May 7, 2025
概括
膜融合依赖于SNARE蛋白和Sec17/Sec18复合体. 第18节ATP水解可以抑制融合,但最佳的融合需要SNARE拉链,第17节和第18节,它们可以独立或一起起作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 膜贩卖 膜贩卖 膜贩卖 膜贩卖
背景情况:
- 细胞内膜融合对细胞过程至关重要,并通过复杂的机制进行介导,包括SNAREs,Rabs,SM蛋白,tethers以及ATPase Sec18/NSF及其辅因子Sec17/SNAP.
- 膜融合是由两个主要机制驱动的:SNARE复杂拉链的完成和Sec17/Sec18复杂的作用,这需要SNARE,但不一定是完全拉链的能量.
研究的目的:
- 为了研究Sec18 ATP水解在膜融合中的作用.
- 为了确定Sec17和Sec18是否与野生型和突变型SNARE一起工作.
- 探索Sec17和Sec18在促进核聚变方面的独立和合作功能.
主要方法:
- 使用纯化的真空蛋白质复制膜融合.
- 在不同条件下对Sec17和Sec18水平,ATP存在和SNARE复合体完整性的融合进行系统分析.
- 在受损SNARE拉链或改变膜特性的情况下评估融合恢复.
主要成果:
- 在较低的Sec17度下,Sec18 ATP水解通过过早释放Sec17来抑制融合,但在更高的Sec17水平或没有ATP水解的情况下,融合会继续.
- 在Sec17,Sec18和ATP (或ATP模拟器) 中,即使使用功能齐全的野生型SNARE和不受阻碍的拉链,也会刺激融合.
- Sec17和Sec18可以独立地促进融合:Sec17恢复了被损坏的拉链阻断的融合,而Sec18则部分挽救了被硬膜抑制的融合.
结论:
- 最佳的膜融合需要SNARE拉链,Sec17和Sec18的协调作用.
- Sec18的ATPase活性起着调节作用,在特定条件下可能抑制融合.
- Sec17和Sec18表现出功能性可塑性,具有协同作用,但也能够对膜融合做出独立贡献.
相关概念视频
ATP Synthase: Structure
11.7K
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
11.7K
ATP Synthase: Mechanism
13.6K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
13.6K
Energy to Drive Translocation
2.0K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.0K
ATP Energy Storage and Release
8.9K
ATP is a highly unstable molecule. Unless quickly used to perform work, ATP spontaneously dissociates into ADP and inorganic phosphate (Pi), and the free energy released during this process is lost as heat. The energy released by ATP hydrolysis is used to perform work inside the cell and depends on a strategy called energy coupling. Cells couple the exergonic reaction of ATP hydrolysis with endergonic reactions, allowing them to proceed.
One example of energy coupling using ATP involves a...
One example of energy coupling using ATP involves a...
8.9K
ATP Driven Pumps II: P-type Pumps
4.4K
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
4.4K
Hydrolysis of ATP
74.2K
The bonds of adenosine triphosphate (ATP) can be broken through the addition of water, releasing one or two phosphate groups in an exergonic process called hydrolysis. This reaction liberates the energy in the bonds for use in the cell—for instance, to synthesize proteins from amino acids.
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine...
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine...
74.2K


