外から内へ,内から外へシグナル伝達におけるインテグリン細胞外ドメインにおけるグローバルコンフォーマーションの再編成
関連する実験動画
Updated: May 6, 2026
06:45
Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
Published on: May 26, 2011
14.6K
Junichi Takagi1, Benjamin M Petre, Thomas Walz
1The Center for Blood Research, Departments of Pathology and Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Cell
|September 17, 2002
まとめ
インテグリンの形状の変化は,スイッチブレードのような開口メカニズムによって明らかにされます. この構造的移行は,リガンド結合またはMn2+によって引き起こされ,リガンドに対するインテグリンの親和性を高めます.
科学分野:
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
背景:
- インテグリン構成とリガンド結合は,細胞結合とシグナル伝達に不可欠です.
- インテグリン活性化の分子メカニズムを理解することは,依然として課題です.
研究 の 目的:
- リガンド結合時にインテグリンの構造変化を解明する.
- 外から内へ,内から外へインテグリンシグナル伝達のメカニズムを調査する.
主な方法:
- 電子顕微鏡による電子顕微鏡
- 物理化学測定 物理化学測定について
- ディスルファイドのクロスリンクによるミュータゲネシス.
- alphaVbeta3およびalphaIIbbeta3インテグリンに対するリガンド結合測定法.
主要な成果:
- 高度な歪みのあるインテグリン構成は,リガンドの afinity が低い.
- リンガン模倣物質またはMn2+) は,インテグリンのスイッチブレードのような拡張を誘導する.
- ハイブリッドドメインとI型ドメインの形状の変化は,リガンド結合と関連しています.
- アルファとベータサブユニット間のC端のクラップの破壊は,インテグリン不屈とリガンド結合を促進します.
結論:
- インテグリン活性化には,曲った状態から拡張状態への劇的な形状の変化が含まれます.
- ハイブリッドドメインの外向きの振動は,リガンド誘発型インテグリン開きにおける重要な出来事である.
- C末端のクラップは,インテグリン適合性と親和性を調節する役割を果たします.
関連する概念動画
01:24Intracellular Signaling Cascades
44.8K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
44.8K
00:59Mechanisms of Membrane Domain Formation
3.2K
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...
3.2K
01:30Assembly of Signaling Complexes
4.7K
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,...
4.7K
01:10Integrins
4.8K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.8K
01:15Activation of Integrins
4.4K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
4.4K
01:17Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K