アスパルテート112は,人間の電圧ゲートプロトンチャネルの選択性フィルターです
Boris Musset1, Susan M E Smith, Sindhu Rajan
1Department of Molecular Biophysics & Physiology, Rush University Medical Center, Chicago, Illinois 60612, USA.
Nature
|October 25, 2011
まとめ
人間の電圧ゲート型陽子チャネル (H(V) 1) は,驚くべき陽子選択性を示しています. この研究では,アスパルテート112がH(V) 1にとって重要なものであることが確認されています.
科学分野:
- バイオフィジックス 生物物理学
- 分子生物学は分子生物学である.
- イオンチャネル機能
背景:
- ポンプとチャネルにおけるイオン選択性は,細胞機能にとって不可欠である.
- 人間の電圧ゲートプロトンチャネル,HVCN1 (HVCN1) は,陽子に対して例外的に選択的です.
- H(V) 1の選択性は,活性酸素種,ヒスタミン分泌,精子容量,呼吸道pHの調節に不可欠です.
研究 の 目的:
- H ((V) 1.1) の異常な陽子選択性の背後にあるメカニズムを解明する.
- H(V) 1の選択性フィルターにおける特定のアミノ酸残留物の役割を調査する.
主な方法:
- H(V) 1チャネルのサイト指向型変異,特にアスパルテート112とアスパルテート185を標的とする.
- ミュータントチャネルの電気生理学的分析により,イオン透過性と選択性を評価する.
- ワイルドタイプと突然変異のH (V) 1チャンネルにおける陽子特異性の比較.
主要な成果:
- アスパルテート112 (Asp112) が中性アミノ酸に変異すると,陽子の特異性が失われ,アニオン選択性または非伝導性が生じます.
- 位112のグルタミン酸変異体は,陽子特異性を保持した.
- アスパルテート185 (Asp185) の変異は,陽子の選択性に影響を与えず,Asp112.2.のユニークな役割を強調しました.
結論:
- アスパルテート112は,H(V) 1の選択性フィルターの不可欠な成分です.
- H(V) 1の陽子特異性のために,選択性フィルターに酸性残留物が必要です.
- この発見は,ヒスティジン基の陽子シャトルメカニズムがH ((V) 1) の選択性に対して異議を唱えている.
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