GTP水解によるHa-Ras p21タンパク質の構造変化の時間解像度X線結晶学的研究
I Schlichting1, S C Almo, G Rapp
1Abteilung Biophysik, Max-Planck-Institut für Medizinische Forschung, Heidelberg, FRG.
Nature
|May 24, 1990
まとめ
GTPの水解後のHa-Ras p21における構造的変化が研究されました. GTP水解はp21の構造変化を誘発し,GTP酶活性化タンパク質との相互作用に影響を与えます.
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.
- 構造生物学 構造生物学とは
背景:
- Ha-Ras p21は,細胞の成長と分化に関与する重要なシグナル伝達タンパク質です.
- GTPの水解は,Rasタンパク質の活性を調節する上で重要なステップです.
- p21の形状の変化を理解することは,その生物学的機能を解読するために不可欠です.
研究 の 目的:
- GTP水解中のHa-Ras p21の構造的動態を調査する.
- p21形状の変化の基礎となる分子機構を解明する.
- これらの構造的変化のトリガーを特定するために.
主な方法:
- ハ-ラスp21の結晶化は,檻に閉じ込められたGTP.
- ラウエ微分法を用いたp21.GTP複合体の構造の決定.
- GTP水解前後の構造的差異の分析.
主要な成果:
- 暫定的なp21.GTP複合体の構造が解明されました.
- GTPase活性化タンパク質と相互作用する領域において,水解後の重要な形状の変化が観察されました.
- 活性部位のMg2+イオンの調整のシフトが誘発因子であると判明した.
結論:
- GTPの水解により,ハラスの構造が大きく変化する p21.
- これらの変化は,GTPase活性化タンパク質との相互作用を調節するために重要である.
- Mg2+イオンの調整状態は,水解結合型コンフォーメーションカスケードを開始する上で重要な役割を果たします.
さらに関連する動画
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...
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...
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
Rab Cascades
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.
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:
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...


