GSDME孔隙形成的结构基础和调节
Evelyn Teran1, Tian Tian1, Chengliang Wang1
1Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT, USA.
Nature communications
|March 14, 2026
概括
气体皮质素E (GSDME) 在细胞死亡过程 - - 热灭过程中形成毛孔. 这项研究揭示了GSDME毛孔结构,并确定了关键的激活步骤,包括caspase-3裂变和棕化,用于其在炎症和癌症中的功能.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 细胞生物学 细胞生物学
背景情况:
- 气体皮膜 (GSDMs) 是关键的孔形成蛋白质,参与热,炎症和癌症.
- 精确的GSDME激活和毛孔组装机制尚未完全理解.
研究的目的:
- 为了阐明人类GSDME孔的高分辨率结构.
- 确定GSDME激活和孔隙形成的分子决定因素.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定GSDME的毛孔结构.
- 结构引导的突变发生来研究蛋白质-脂质和蛋白质-蛋白质相互作用.
- 生物化学测试以评估GSDME的激活和功能.
主要成果:
- 确定了27倍和28倍的人类GSDME毛孔的高分辨率冷EM结构.
- 识别了保存的结构特征和独特的膜接触几何形状.
- 发现caspase-3在DMPD基因上切割GSDME,而S-palmitoylation通过Cys180.0增强孔隙形成.
结论:
- GSDME 孔隙形成是由一个连续的过程,包括蛋白质分解活性和脂质修饰调节.
- 这些发现为了解GSDME在炎症和癌症相关过程中的功能提供了一个框架.
更多相关视频
09:54Multifunctional, Micropipette-based Method for Incorporation And Stimulation of Bacterial Mechanosensitive Ion Channels in Droplet Interface Bilayers
Published on: November 19, 2015
11.2K
09:43Fine-tuning the Size and Minimizing the Noise of Solid-state Nanopores
Published on: October 31, 2013
14.3K
相关概念视频
GTPases and their Regulation
10.2K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
10.2K
Activation and Inactivation of G Proteins
12.1K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
12.1K
Mechanisms of Membrane Domain Formation
4.3K
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...
Another mechanism for membrane domain formation involves membrane proteins interacting with...
4.3K
Pore Size Distribution
555
In concrete, the pore size distribution significantly influences the material's properties. Capillary pores, markedly larger than gel pores, form a vast network within partially hydrated cement paste, reducing the concrete's strength and increasing its permeability. This heightened permeability leads to a greater risk of damage from environmental factors like freeze-thaw cycles and chemical attacks, with the extent of vulnerability also being tied to the water-to-cement ratio.
Adequate...
Adequate...
555
Mechanism of Lamellipodia Formation
3.9K
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
3.9K
IP3/DAG Signaling Pathway
15.6K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
15.6K
