システインプロテアゼインタールイキン-1β変換酵素の結晶構造:a (p20/p10) 2ホモジマー
N P Walker1, R V Talanian, K D Brady
1BASF Aktiengesellschaft, Main Laboratory, Ludwigshafen, Federal Republic of Germany.
Cell
|July 29, 1994
まとめ
インタールイキン-1β変換酵素 (ICE) は,アポトーシスに不可欠なプロテアゼです. その結晶構造は,触媒ドメインのホモダイマーを示し,プログラムされた細胞死経路に関する新しい洞察を示唆しています.
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.
- 構造生物学 構造生物学とは
背景:
- インタールイキン-1β変換酵素 (ICE) は,プロIL-1βをプロテオリチス的に活性化して活性化します.
- ICEは,C. elegansの細胞死遺伝子産物であるCED-3と同型である.
- ICE/CED-3ファミリーのメンバーは,プログラム細胞死 (アポトーシス) に関与しています.
研究 の 目的:
- 再結合ヒトICE-テトラペプチドクロロメチルケトン複合体の結晶構造を決定する.
- ICEホロ酵素の組立と活性化の構造的基礎を解明する.
- ICE/CED-3プロテアゼファミリー内の機能的類似性を調査する.
主な方法:
- 2.5Aの解像度のX線結晶学.
- リコンビナンスのヒトICE-テトラペプチドクロロメチルケトン複合体の分析.
主要な成果:
- ホロ酵素は,それぞれp20およびp10サブユニットで構成される触媒ドメインのホモダイマーです.
- p20のC端末とp10のN端末の空間的な分離は,他の in vivo アセンブリと活性化経路を示唆しています.
- ICE/CED-3ファミリーのメンバー間の活性部位残留物の保存は,共有された機能的メカニズムを示しています.
結論:
- 結晶構造は,ICEのホモジメル組織についての洞察を提供します.
- この発見は,ICEの組み立てと in vivo の活性化のための新しい経路を示唆しています.
- ICEとCED-3は,アポトーシスに不可欠な細胞質システインプロテアースの新種のクラスを表しています.
さらに関連する動画
関連する概念動画
Protein Folding
Overview
Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
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Many viruses self-assemble into a fully functional unit using the infected host cell to...
Protein-protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...


