Gタンパク質結合受容体は,モデルバイレイヤのダイナミクスシミュレーションで自己組み立てを行う
Xavier Periole1, Thomas Huber, Siewert-Jan Marrink
1Groningen Biomolecular Sciences and Biotechnology Institute, Department of Biophysical Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands. x.periole@rug.nl
Journal of the American Chemical Society
|July 31, 2007
まとめ
膜タンパク質の自己組み立て,特にGタンパク質結合受容体 (GPCRs) の自己組み立ては,フォスフォリピド二重層の特性によって影響を受けます. 超膜ヘリクスの近くの局所的な膜変形は,タンパク質の結合率と方向性を決定する.
科学分野:
- バイオフィジックス 生物物理学
- コンピュータ生物学 コンピュータ生物学
- 膜タンパク質のダイナミクス
背景:
- Gタンパク質結合受容体 (GPCR) を含む統合膜タンパク質は,オリゴメリック構造を形成する.
- 膜におけるGPCR自己組み立てのメカニズムと生理学的意義は,依然としてほとんど不明である.
研究 の 目的:
- 視覚的なロドプシン自己組み立ての分子基盤を調査する.
- フォスフォリピド二重層の性質がGPCRの自己組み立てにどのように影響するか,計算モデルを使用して決定する.
主な方法:
- 大規模シミュレーションのための粗粒子分子動力学 (CGMD) モデルを使用した.
- 最大16個のロドプシン分子を1:100のタンパク質対脂質比で8マイクロ秒間シミュレートしたシステム.
- 4つの異なるフォスフォリピド環境を分析した.
主要な成果:
- トランスメブランヘリックス2,4,7の近くで再現可能な局所化された膜二層の適応を特定しました.
- 局所的な膜変形がタンパク質とタンパク質の関連性にとって重要であることが示された.
- 膜の性質が,ロドプシン集合の速度,範囲,方向を決定することを示した.
結論:
- 局所的な膜変形は,膜タンパク質の自己組織化における重要な要因である.
- 発見は,膜タンパク質のオリゴメリゼーションの一般的なメカニズムについての洞察を提供します.
- 膜の物理化学的性質とタンパク質組立のダイナミクスとの関連を示唆する.
関連する概念動画
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.
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,...
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...
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...


