イノシトール1,4,5-トリスホスファート受容体結合核の構造は,そのリガンドとの複合体で
Ivan Bosanac1, Jean-René Alattia, Tapas K Mal
1Division of Molecular and Structural Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
Nature
|November 21, 2002
まとめ
イノシトール1,4,5-トリフォスファート (InsP3) 受容体 (InsP3R) の結合核の結晶構造は,ブーメラングの形とカルシウム (Ca2+) の結合とInsP3の調整のための重要な残留物を明らかにします. この発見は,細胞の信号伝達経路についての理解を深める.
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.
- 細胞生物学 細胞生物学
背景:
- イノシトール1,4,5-トリフォスファート (InsP3) 受容体 (InsP3R) は,様々な細胞プロセスに関与するエンドプラズマ網膜のCa2+放出チャネルである.
- InsP3R1は,小脳プルキンジェ細胞に豊富に存在し,InsP3結合,調節,チャネル領域が異なっている.
研究 の 目的:
- マウスのInsP3R1.1.1のInsP3結合核の結晶構造を決定する.
- InsP3結合とCa2+調整の構造的基礎を解明する.
主な方法:
- X線結晶学を用いて2.2 Åの解像度構造が得られた.
- この構造は,マウス InsP3R1 の InsP3 結合コアと InsP3.3 の複合体で決定された.
主要な成果:
- InsP3結合コアは,不対称でブーメラングのような構造を示しています.
- N端のベータ・トリフォイル・ドメインと,C端のアルファ・ヘリカル・ドメインで構成され,アーマディロ・リピート型の折りたたみがあります.
- ドメイン間の裂け目には,InsP3のリン酸化基を調整するアルギニンとライシン残基が含まれ,推定Ca2+結合部位が特定されました.
結論:
- 決定された構造は,InsP3結合部位の分子構造の詳細な洞察を提供します.
- この構造情報は,InsP3媒介カルシウムシグナル伝達とInsP3R機能を理解するために不可欠です.
関連する概念動画
Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Ligand-gated Ion Channels
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Ligand-gated Ion Channels
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...


