カルシウムポンプの結晶構造は,結合されたATPアナログを持つ
Chikashi Toyoshima1, Tatsuaki Mizutani
1Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan. ct@iam.u-tokyo.ac.jp
Nature
|July 2, 2004
まとめ
この研究は,骨格筋のカルシウム (Ca2+) ポンプの結晶構造を明らかにし,ATP結合がドメインの再編成を引き起こす方法を詳細に説明しています. このメカニズムは,Ca2+イオンがオクラージュされ,サルコプラズマ網膜に放出されるための準備をどのようにしているかを説明します.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- 分子生理学 分子生理学
背景:
- P型ATPアゼは,細胞膜の間のイオングラデントを維持するATP駆動型イオンポンプである.
- 骨格筋のサルコプラズマ網膜にあるCa2+ポンプは,P型ATPアザススーパーファミリーの重要な代表である.
研究 の 目的:
- サルコプラズマ網膜のCa2+ポンプによるCa2+閉塞と輸送の構造的メカニズムを解明する.
- ATP結合とイオン相互作用によって誘発される形状の変化を記述する.
主な方法:
- X線結晶学を用いて,Ca2+ポンプの構造を決定した.
- 構造は,ATPのアナログであるMg2+とCa2+イオンの存在で解かれた.
主要な成果:
- ATPのアナログは,NとPの細胞質ドメインを橋渡しし,ポンプの構造を再編成します.
- ATPアナログとMg2+の結合により,Pドメインの構造が変化し,Aドメインの傾きが生じます.
- この形状の変化は,超膜領域内のCa2+イオンの遮断につながります.
結論:
- 決定された構造は,輸送前にCa2+イオンオクラージョンのメカニズムを洞察します.
- この研究は,P型ATPアゼイオン輸送サイクルにおける重要なステップを明らかにしています.
- この発見は,細胞生理学におけるイオンポンプの機能を理解するのに役立つ.
関連する概念動画
01:29Primary Active Transport
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they would not...
01:27ATP Driven Pumps I: An Overview
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
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01:48ATP Synthase: Mechanism
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
01:18ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
01:34ATP Driven Pumps II: P-type Pumps
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
01:30ATP Driven Pumps III: V-type Pumps
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The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...