Smac/DIABLOをXIAP BIR3ドメインに結合するための構造的基礎
1Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Nature
|January 5, 2001
まとめ
Smac (DIABLO) がアポトーシス阻害タンパク質 (IAP) に結合することは,カスペスの活性化に不可欠です. この研究は,XIAPのBIR3ドメインに結合するSmacペプチドの構造を明らかにし,がん治療の開発を支援しています.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- 分子生物学は分子生物学である.
背景:
- アポプトーシス阻害タンパク質 (IAP) は,プログラム細胞死の主な調節体であり,カスペスを阻害します.
- Smac (DIABLO) は,IAPに敵対し,カスパース活性化とアポトーシスを促進する.
- SmacのN端残基は,その機能に不可欠ですが,IAP結合における構造的役割は不明です.
研究 の 目的:
- Smac と IAP の間の分子認識の構造的基礎を解明する.
- Smac由来ペプチドで複合されたXIAPのBIR3ドメインの溶液構造を決定する.
主な方法:
- 核磁共振 (NMR) スペクトロスコピーは,溶液の構造を決定する.
- SmacペプチドとXIAP BIR3ドメインの相互作用を分析するためのサイト誘導性変異.
主要な成果:
- 9つの残基のSmacペプチドは,XIAP BIR3ドメインの第3ベータ鎖に結合する拡張形状を採用しています.
- SmacペプチドのN末端の4つの残基のみが,BIR3ドメインと直接相互作用する.
- 複合体は,水素結合,静電相互作用,水害性相互作用によって安定化される.
結論:
- 決定された構造は,Smac-IAP分子認識に関する重要な洞察を提供します.
- この構造情報は,がん治療のためのIAPを標的とする小分子設計を導くことができます.
さらに関連する動画
10:17Creating Highly Specific Chemically Induced Protein Dimerization Systems by Stepwise Phage Selection of a Combinatorial Single-Domain Antibody Library
Published on: January 14, 2020
8.2K
10:28Expression, Purification, and Liposome Binding of Budding Yeast SNX-BAR Heterodimers
Published on: December 6, 2019
8.2K
関連する概念動画
01:30Assembly of Signaling Complexes
6.4K
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,...
6.4K
01:49Conserved Binding Sites
5.0K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.0K
01:20The JAK-STAT Signaling Pathway
11.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
11.7K