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Updated: Aug 13, 2026

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Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
細胞外gp130サイトカイン受容体信号伝達複合体の構造
1Department of Microbiology and Immunology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305, USA.
まとめ
カポシのサルコマ関連ヘルペスウイルスは,ヒトのgp130.0.を活性化するウイルス性インターリューキン-6 (IL-6) をコードする. ウイルスのIL-6は,ヒトのIL-6とは異なり,結合を強化するために,水性相互作用を使用します.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- ウイルス学 ウイルス学 ウイルス学
背景:
- gp130は,リガンド結合と複合性オリゴメリゼーションによって活性化されるサイトカインの信号伝達受容体です.
- カポシの肉腫関連ヘルペスウイルス (KSHV) は,ヒトのgp130.0.を活性化するウイルスIL-6同型を生成します.
研究 の 目的:
- ウイルスのIL-6結合とヒトgp130.0.の活性化の構造的基礎を解明する.
- 宿主サイトカインシグナル伝達のKSHVの操作の基礎にある分子機構を理解する.
主な方法:
- ウイルスIL-6/gp130複合体の2.4アングストームの構造を決定するために,X線結晶学を用いた.
- 信号アセンブリ内のタンパク質-タンパク質相互作用と結合インターフェースの分析.
主要な成果:
- 結晶構造は,2つのウイルスIL-6/gp130ユニットによって形成されたテトラメリック複合体を明らかにしました.
- gp130免疫グロブリン領域とウイルスIL-6サイトIIIの間の直接的な相互作用は,受容体の活性化にとって極めて重要です.
- ウイルスのIL-6は,gp130結合のために水性アミノ酸を使用し,ヒトIL-6の水性相互作用と比較して,インターフェースの互換性を強化します.
- gp130のアンフィパティック結合部位は,可塑性を発揮し,ウイルスIL-6との交叉反応に寄与する.
結論:
- この研究では,ウイルスのIL-6がヒトのgp130を特定の水性相互作用によって活性化させる構造的メカニズムが明らかにされています.
- この発見は,宿主信号伝達経路を乗っ取るためのウイルス適応戦略を強調しています.
- これらの相互作用を理解することで,ウイルスサイトカイン同種を標的とした治療戦略を策定することができます.
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.
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 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...
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...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...

