GSDMBの孔形成の構造的基礎とIpaH7.8による標的化
Chengliang Wang1, Sonia Shivcharan1, Tian Tian1
1Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT, USA.
Nature
|March 29, 2023
まとめ
シゲラ
科学分野:
- 分子生物学
- 免疫学
- 構造生物学
背景:
- ガスダーミン (GSDM) は,宿主防御機構である熱死に不可欠な孔を形成するタンパク質です.
- GSDMBの独特の特性と発火性の可能性は議論されているが,直接的な殺菌活性を示している.
- Shigellaは,GSDMBを分解するエフェクタ IpaH7.8 を介して,GSDMBによる防御を回避する.
研究 の 目的:
- Shigella IpaH7.8の認識とGSDMBの標的化に関する構造的根拠を解明する.
- GSDMBの毛穴形成と炎症性の活性に関する構造的調節を調査する.
主な方法:
- 低温電子顕微鏡 (cryo-EM) を用いて,GSDMB- IpaH7. 8複合体とGSDMB孔の構造を決定した.
- 構造分析により,タンパク質とタンパク質の相互作用と調節に関与する主要な残留物とモチーフが特定されました.
主要な成果:
- 凍結EM構造は,Shigella IpaH7.8によって認識されたGSDMBの3つの負の電荷の残留物のモチーフを明らかにし,種特異性を説明しました.
- GSDMBの毛穴構造は,ピロプトーシス活性調節における代替スプライシング調節型インタードメインリンクナーの役割を強調した.
- カノニカルリンカーを持つGSDMBイソフォームは正常なピロプトーシスを示したが,他のものは活動が弱まったか全くなかった.
結論:
- この研究は,Shigella IpaH7.8がGSDMBを標的とする分子機構を明らかにしています.
- GSDMBの特定の構造モチーフは,IpaH7.8の認識に不可欠であり,種特異性を決定する.
- GSDMBのインタードメインリンクの代替スプライシングは,そのパイロプトティック機能に大きく影響します.
関連する概念動画
IP3/DAG Signaling Pathway
12.2K
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...
12.2K
Coat Assembly and GTPases
3.6K
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...
3.6K
Mechanism of Lamellipodia Formation
2.7K
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...
2.7K
GPI Anchoring of Proteins in the ER Membrane
4.2K
GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
4.2K
Structure of Porins
3.1K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
3.1K
Mechanism of Filopodia Formation
2.4K
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...
2.4K


