EGF受容体の活性化において,プラズマ膜を横断する適合結合
Nicholas F Endres1, Rahul Das, Adam W Smith
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell
|February 5, 2013
まとめ
皮膚表皮成長因子受容体 (EGFR) の活性化は,その表面密度に依存する. EGF結合はステリック制約を解除し,トランスメブランヘリックス相互作用と受容体の活性化を促進します.
科学分野:
- バイオケミストリー バイオケミストリー
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
背景:
- 皮膚表皮成長因子受容体 (EGFR) の活性化メカニズムは完全に理解されていません.
- EGFRの細胞内領域は,溶液中の固有の活性を示します.
研究 の 目的:
- EGFR活性化の調節を調査する.
- EGFRの表面密度の自己リン酸化における役割を決定する.
主な方法:
- 細胞の表面密度の関数としてEGFR自己リン酸化の測定.
- ディメリゼーションを評価するために,光交差相関スペクトロスコーピー.
- 核磁共振 (NMR) と機能的測定法. 核磁共振 (NMR) と機能的測定法. 核磁共振 (NMR) と機能的測定法. 核磁共振 (NMR) と機能的測定法. 核磁共振 (NMR) と機能的測定法.
主要な成果:
- EGFRは,EGFなしで高表面密度でのみ抑制から逃れることができます.
- トランスメブランヘリックスと細胞内モジュールは,共同で構成的活動を可能にします.
- 隔離された細胞内モジュールは不活性化され,膜に結合すると二元化することができません.
- アクティベーションには,N端のトランスメブランヘリックス相互作用が必要であり,柔膜セグメントの相互作用と膜の解放を促進します.
結論:
- EGFの結合は,細胞外硬化制約を緩和する.
- これは,トランスメブランヘリクスのN端結合経由での活性化を促します.
- EGFRの活性化は,リガンド結合と受容体の表面密度の両方によって調節されます.
関連する概念動画
Amplifying Signals via Second Messengers
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Assembly of Signaling Complexes
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,...
Activation and Inactivation of G Proteins
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 affinity and are together...
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
Cell-surface Signaling
Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.


