リボソームのGTP水解の活性化メカニズム
Rebecca M Voorhees1, T Martin Schmeing1, Ann C Kelley1
1MRC Laboratory of Molecular Biology, Cambridge, UK, CB2 0QH.
まとめ
研究者らは,タンパク質合成において,リボソームがGTPの水解をどのように活性化するかを明らかにした. 結晶構造は,アミノアシル-tRNAsの配分に不可欠なアクティブな形状の延長因子Tu (EF-Tu) を示しています.
科学分野:
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
- バイオケミストリー バイオケミストリー
背景:
- タンパク質合成は,延長因子Tu (EF-Tu) のようなグアノシントリフォスファターゼ (GTPase) 因子に依存しています.
- EF-Tuは,アミノアシル転送RNA (tRNA) を翻訳中にリボソームに提供する.
- リボソームによるGTPaseの活性化を理解することは,タンパク質合成の調節を解読する鍵です.
研究 の 目的:
- リボソームがトランスレーション性GTP相でGTP水解を誘発するメカニズムを解明する.
- リボソームにおけるEF-Tu活性化の構造的基礎を決定する.
主な方法:
- 構造を決定するために,X線結晶学を用いた.
- リボソームに結合するEF-Tuとアミノアシル-tRNAの構造は,GTPアナログを使用して3.2アングストームに解明されました.
主要な成果:
- EF-Tuは,その活性形状で観察されました.
- EF-TuのスイッチIループを注文し,GTPの水解のために触媒ヒスティジンを配置しました.
- ヒスティジンと23SリボソームRNAのサルシン-リシンループのA2662との間の保存された相互作用は,活性化にとって重要なものとして特定されました.
結論:
- 決定された構造は,翻訳性GTPasesの活性化メカニズムについての洞察を提供します.
- リボソームのGTPase活性化と水解の普遍的なメカニズムが示唆されています.
- この発見は,タンパク質合成の複雑なプロセスについての理解を深める.
関連する概念動画
GTPases and their Regulation
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, also known...
Large G-proteins, also known...
GTPases and their Regulation
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, also known...
Large G-proteins, also known...
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...
Small GTPases - Ras and Rho
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:
Rab Proteins
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...
Mechanical Protein Functions
Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.


