二重層のGタンパク質結合受容体の超分子組織の構造的決定因子
Xavier Periole1, Adam M Knepp, Thomas P Sakmar
1Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands. x.periole@rug.nl
Journal of the American Chemical Society
|June 12, 2012
まとめ
Gタンパク質結合受容体 (GPCR) ロドプシンが細胞膜に安定したジマーを形成する. 分子ダイナミクスシミュレーションは,特定のヘリックス相互作用によって誘発される好ましい尾から尾の形状を明らかにし,これはGPCRを理解するために不可欠です.
科学分野:
- バイオフィジックス 生物物理学
- 構造生物学 構造生物学とは
- コンピュータ生物学 コンピュータ生物学
背景:
- ロドプシンのようなGタンパク質結合受容体 (GPCRs) は,本来の膜で自己組織化します.
- GPCR オリゴメリゼーションの構造的基礎は,依然としてほとんど不明である.
- これらの相互作用を理解することは,GPCRの機能の鍵です.
研究 の 目的:
- ロドプシンが自己組織化して超分子構造を形成する構造的決定因子を解明する.
- ロドプシンの好ましい相互作用モードと安定した二重体構成を特定するために.
- 超膜タンパク質二分化を研究するための一般的な計算戦略を確立する.
主な方法:
- モデル膜におけるロドプシンの粗粒線分子動力学 (CGMD) シミュレーション.
- シミュレーションは100μsまで拡張され,最大64個のロドプシン分子が含まれています.
- 受容体-受容体相互作用を分析するために,平均力 (PMF) 計算の傘サンプリングとポテンシャル.
主要な成果:
- ロドプシン分子間の強い好ましい相互作用モードを特定しました.
- 安定した二重体形成のためのエネルギー障壁のない受容体-受容体相互作用の2つの主要なモードを明らかにした.
- 好ましいロドプシン二重体は,トランスメブランヘリックスH1/H2とアンフィパシーヘリックスH8.8を含む尾から尾の形状を採用しています.
結論:
- ロドプシンは,実験データと一致する,尾から尾の方向に安定したジマーを形成します.
- 安定性が低い脂質で覆われたダイマーは,ヘリックスH4とH6の相互作用によって安定する.
- CGMDアプローチは,GPCRおよび他のトランスメブランタンパク質の二酸化を研究するのに適用できます.
関連する概念動画
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...
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
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,...
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.


