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ヘッジホッグの自己処理ドメインの結晶構造:ヘッジホッグと自己結合タンパク質のホモロジー
T M Hall1, J A Porter, K E Young
1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cell
|October 23, 1997
まとめ
ドロソフィラ・ヘッジホッグのタンパク質 (Hh-C) のカルボキシ末端ドメインは,自己処理を受けます. その結晶構造は,同類のサブドメインを明らかにし,ヘッジホッグタンパク質の進化とインテインの保存に関する洞察を提供します.
科学分野:
- 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
- 進化生物学の進化生物学について
背景:
- ドロソフィラ・ヘッジホッグ (Drosophila Hedgehog) タンパク質 (Hh-C) のカルボキシ末端ドメインは,自己処理活性を示しており,これは活性信号形式を生成するのに極めて重要です.
- このプロセスは,分子内裂とコレステロールがアミノ端末断片に結合することを含む.
研究 の 目的:
- Hh-C (Hh-C17) の活性17 kDaの断片の結晶構造を決定する.
- Hh-C17活性部位における主要な残基を特定し,自動処理におけるその役割を明らかにする.
- Hh-Cとインテインの進化的関係を探求する.
主な方法:
- Hh-C17の断片の浄化と結晶化.
- Hh-C17の3D構造を決定するためのX線結晶学.
- 活性部位残留物の機能を調べるために,部位指向型変異を生成する.
主要な成果:
- Hh-C17の結晶構造が決定され,遺伝子の複製から発生した可能性が高い2つの同類サブドメインが明らかになりました.
- ヘッジホッグの自動処理に関与する主要な活性部位残基が特定されました.
- Hh-C17とインテインの間の保存された特徴は,共通の進化的起源を示唆しています.
結論:
- Hh-C17の構造は,ヘッジホッグの自動処理を理解するための分子基盤を提供します.
- この発見は,ヘッジホッグタンパク質ドメインとインテインの間の妥当な進化的リンクを示唆しています.
- この研究は,タンパク質のスプライシングメカニズムの進化についての洞察を提供します.
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