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Small GTPases - Ras and Rho
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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
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Rab Proteins
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Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
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Protein Modifications in the RER
7.6K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
7.6K
Regulation of Nuclear Protein Sorting
3.5K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Rab Cascades
3.8K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Export of Misfolded Proteins out of the ER
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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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サイトソリック拡張は,基板のゲーティングゲートを調節することによって,ロンボイドプロテアスを直接調節します.
Rosanna P Baker1, Siniša Urban1
1Howard Hughes Medical Institute, Department of Molecular Biology &Genetics, Johns Hopkins University School of Medicine, Room 507 PCTB, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
Nature
|May 14, 2015
まとめ
カルシウムイオンは,基板ゲーティングを制御することによって,膜内タンパク質酵素,特にロンボイド-4を調節する. この発見は,細胞シグナル伝達と疾患に関連するプロテアゼ機能に関する新しい洞察を提供します.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- 内膜プロテアゼは細胞シグナル伝達に不可欠であり,疾患に関与しています.
- これらの膜結合酵素の直接的調節メカニズムについては,依然としてほとんど不明である.
研究 の 目的:
- 膜内プロテアゼの直接調節を調査し,カルシウム結合EF手を持つロンボ状プロテアゼに焦点を当てました.
- ロンボタンパク質酵素の活性と基板加工におけるカルシウムの役割を明らかにする.
主な方法:
- ドロソフィラ細胞におけるカルシウム結合ロンボイドプロテアゼ (ロンボイド-4) の特徴.
- カルシウム依存タンパク質分解を研究するために,ロンボイド-4の浄化とリポソーム再構成.
- 制御領域を特定するために,細胞プラズマループのEFハンド削除と変異の分析.
主要な成果:
- カルシウムは,細胞系と再構成系の両方で,ロンボイド-4によるタンパク質分解を強く刺激する.
- EF-ハンドドメインは早めのタンパク質分解を防止するために不可欠であり,細胞プラズマループはカルシウム誘発刺激を媒介する.
- 調節はカルシウム媒介による基板ゲート化によって起こりますが,ジメリゼーションや基板相互作用ではありません.
結論:
- サブストラットゲーティングは,膜内プロテオリシスのための進化した規制メカニズムであり,触媒自体には不可欠ではありません.
- カルシウムは,基板のゲーティングを通じて,ロンボイドプロテアースの活性を直接調節する作用をします.
- これらの発見は,ロンボイドプロテアゼの機能と上流の規制インプットの研究のための新しい道を開きます.


