リジスティン系ホルモンのジスルファイド依存型マルチメリック組成
Saurabh D Patel1, Michael W Rajala, Luciano Rossetti
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Science (New York, N.Y.)
|May 25, 2004
まとめ
肥満と糖尿病に関連したホルモンであるレジスティンは,ヘクサマーとトリマーとして循環しています. レジスティントリマーのジスルファイド結合の破壊は,そのインスリン感受性の効果を高め,重要な活性化ステップを示唆する.
科学分野:
- バイオケミストリー バイオケミストリー
- エンドクリノロジー エンドクリノロジー
- 構造生物学 構造生物学とは
背景:
- レジスティンは脂肪細胞によって分泌されるホルモンです.
- 肝臓におけるインスリン作用に逆らいます.
- レジスティンは,肥満と糖尿病を結びつける可能性がある.
研究 の 目的:
- レジスティンのマルチメリック構造を調査する.
- レジスティンの機能におけるディスルファイド結合の役割を決定する.
- レジスティンの活性化メカニズムを探求するために.
主な方法:
- レジスティンとRELMbetaの構造を決定するために,X線結晶学を用いた.
- 血清サンプルを分析して,レジスティンの組立状態を特定しました.
- 臓・インスリン・クランプの研究は,野生型および変異性耐性菌を用いて行われた.
主要な成果:
- レジスティンとRELMbetaは,ヘッドとテールドメインを持つ珍しいマルチメリック構造を示しています.
- レジスティンは,コイル・コイル相互作用とジスルファイド結合を通じてヘクサマーを形成する.
- レジスティンはヘキサマーとトリマー形式で循環する.
- インタートリマー二酸化硫化物結合が欠けているレジスティン突然変異体は,肝臓のインスリン感受性の向上を示した.
結論:
- レジスティンの構造は,ヘクサマーを形成するコイル・コイル・アルファ・ヘリカルセグメントを含む.
- ディスルファイド結合処理は,レジスティンの活性化に不可欠です.
- レジスティンの構造と活性化の理解は,糖尿病に対する新しい治療目標を提供することができます.
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