二重層のH-rasタンパク質:相互作用と構造の混乱
Alemayehu A Gorfe1, Arneh Babakhani, J Andrew McCammon
1Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, and Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0365, USA.
Journal of the American Chemical Society
|September 21, 2007
まとめ
Ras GTPasesは,脂質の改変によって細胞膜に固定されます. この研究は,脂質二重層とのH-ras相互作用を詳細に説明し,アンカー特性が膜組織とナノクラスター形成にどのように影響するかを明らかにしています.
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.
- バイオフィジックス 生物物理学
背景:
- Ras GTPasesは,機能するために膜アンカリングを必要とします.
- 細胞分裂,発育,がんにおける彼らの役割は重要だ.
- 膜の挿入と複雑な構造の正確なメカニズムは不明である.
研究 の 目的:
- H-ras膜アンカーとDMPCバイレイヤーの間の原子相互作用を調査する.
- H-ras膜結合の構造的基礎を解明する.
- H-rasが膜ナノクラスター組織にどのように貢献するのかを理解するために.
主な方法:
- DMPCバイレイヤーの全長H-rasタンパク質構造の計算による特徴付け.
- タンパク質-脂質界面における原子相互作用の詳細な分析.
主要な成果:
- パルミトイロ化システインとMet182は,水素結合とヴァン・デル・ワールスの相互作用を通じて膜親和に寄与する.
- の極側鎖は,二重層内の方向性を安定させる.
- ローカライズされた二重層の混乱が観察され,アンカー挿入の深さとローカライゼーションに依存し,触媒ドメインとリンクヤーによって調節されます.
結論:
- 特定の水素結合とアンカーの柔軟性は,ras-DMPCの相互作用モードを決定する.
- Ras GTPaseが膜ナノクラスター組織に関与していることの構造的証拠を提供します.
- Ras GTPaseの膜ダイナミクスと機能の理解を深める.
関連する概念動画
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...
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...
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.
Multi-pass Transmembrane Proteins and β-barrels
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...

