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08:33
Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
Published on: March 11, 2021
閉じた状態のATPゲート型P2X(4) イオンチャネルの結晶構造
Toshimitsu Kawate1, Jennifer Carlisle Michel, William T Birdsong
1Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Oregon 97239, USA.
Nature
|July 31, 2009
まとめ
P2X受容体に関する構造的な洞察は,その杯状のトリメア形と新しいATP結合部位を明らかにします. この研究は,ATP結合がこれらの重要なイオンチャネルをどのように開くかを理解するための分子基盤を提供します.
科学分野:
- バイオフィジックス 生物物理学
- 構造生物学 構造生物学とは
- 神経科学は神経科学である.
背景:
- P2X受容体は,細胞外ATPによってゲートされたカチオンチャンネルであり,重要な生理学的プロセスに関与しています.
- 彼らのユニークな構造には,既知のイオンチャネルタンパク質ホモロジーがないため,ゲーティングメカニズムの理解を妨げています.
研究 の 目的:
- ゼブラフィッシュの静止状態のP2X(4) 受容体の分子構造を解明する.
- リガンドゲッティングとイオン浸透を含むP2X受容体の機能を理解するための構造的基礎を提供すること.
主な方法:
- ゼブラフィッシュのP2X(4) 受容体の構造を決定するために,X線結晶学を用いた.
- トリメア構造,サブユニットインターフェース,および毛穴領域の分析.
主要な成果:
- ゼブラフィッシュのP2X(4) 受容体は,杯の形状のトライマー形状を採用しています.
- 3つの非正規の,サブユニット間のATP結合部位を特定しました.
- 超膜領域内のイオンチャネルゲートを特徴づけた.
結論:
- 決定された構造は,P2X受容体のゲーティングとアセンブリのための分子基盤を提供します.
- ATP結合は,おそらく形状の変化を誘導し,イオンチャネル開通につながります.
- これらの発見は,P2X受容体の多様な生理学的役割を理解するために重要である.
関連する概念動画
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...
02:42Ionic Crystal Structures
Ionic crystals consist of two or more different kinds of ions that usually have different sizes. The packing of these ions into a crystal structure is more complex than the packing of metal atoms that are the same size.
Most monatomic ions behave as charged spheres, and their attraction for ions of opposite charge is the same in every direction. Consequently, stable structures for ionic compounds result (1) when ions of one charge are surrounded by as many ions as possible of the opposite...
Most monatomic ions behave as charged spheres, and their attraction for ions of opposite charge is the same in every direction. Consequently, stable structures for ionic compounds result (1) when ions of one charge are surrounded by as many ions as possible of the opposite...
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...
01:30Ligand-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...
02:46Crystal Field Theory - Tetrahedral and Square Planar Complexes
Tetrahedral Complexes
Crystal field theory (CFT) is applicable to molecules in geometries other than octahedral. In octahedral complexes, the lobes of the dx2−y2 and dz2 orbitals point directly at the ligands. For tetrahedral complexes, the d orbitals remain in place, but with only four ligands located between the axes. None of the orbitals points directly at the tetrahedral ligands. However, the dx2−y2 and dz2 orbitals (along the Cartesian axes) overlap with the ligands less than the dxy,...
Crystal field theory (CFT) is applicable to molecules in geometries other than octahedral. In octahedral complexes, the lobes of the dx2−y2 and dz2 orbitals point directly at the ligands. For tetrahedral complexes, the d orbitals remain in place, but with only four ligands located between the axes. None of the orbitals points directly at the tetrahedral ligands. However, the dx2−y2 and dz2 orbitals (along the Cartesian axes) overlap with the ligands less than the dxy,...