孔構造と酸感知イオンチャネルとP2X受容体のイオン部位

Eric B Gonzales¹, Toshimitsu Kawate, Eric Gouaux

¹Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.

Nature

|July 31, 2009

まとめ

この研究は,痛みや味覚などの機能に不可欠な酸感受性イオンチャネルの構造を明らかにしています. 発見は,チャネルを明らかにします.

科学分野:

構造生物学構造生物学とは
イオンチャンネル生理学イオンチャンネル生理学
分子神経科学は分子神経科学である.

背景:

酸感知イオンチャネル (ASIC) は,重要な生理学的プロセスに関与する,陽子活性化,ナトリウム選択性チャネルである.
ナトリウムホメオスタシス,味,痛みにおけるその重要性にもかかわらず,ASIC機能の構造的基礎は依然として十分に理解されていません.
独特のトリメア亜単位の組成は,構造的決定に課題を提示しています.

研究の目的:

機能的な酸感知イオンチャネルの高解像度構造を解明する.
チャンネル内の無感化ゲートの構造的特徴を特定する.
イオン結合部位とチャネル前庭内の調整を調査する.

主な方法:

酸感知イオンチャネルの構造を決定するために,X線結晶学を用いた.
高解像度 (3 Å) の構造分析が行われました.
イオン調整を理解するためにセシウムイオン結合を分析した.

主要な成果:

不感受状態の機能的な酸感受イオンチャネルの3 Å解像度構造が決定されました.
脱感ゲートは局所化し,約8 Å 厚さの構造体として特徴付けられました.
細胞外ベスティビュールのセシウムイオンの三角反プリズム調整が観察されました.

結論:

決定された構造は,酸感知イオンチャネルのアーキテクチャに関する前例のない洞察を提供します.
酸感受性イオンチャネルとATPゲート型P2X4受容体,特に毛穴構造の構造的な類似性が指摘されました.
これらの発見は,イオンチャネル機能を支配する共通の,まだ以前に認識されていない構造的および機械的原理を示唆しています.

さらに関連する動画

11:47

Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells

Published on: April 3, 2019

08:33

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time

Published on: March 11, 2021

関連する概念動画

01:19

Ion Channels

The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...

01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.

01:19

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...

01:12

Mechanically-gated Ion Channels

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...

01:24

Non-gated Ion Channels

01:32

Postsynaptic Potential (PSP)

Postsynaptic potential (PSP) refers to a change in the electrical potential of a neuron when neurotransmitters released by presynaptic neurons bind to postsynaptic receptors. This potential can either be excitatory, leading to depolarization and ultimately action potential generation, or inhibitory, leading to hyperpolarization and suppression of the postsynaptic neuron.
There are two types of receptors: ionotropic and metabotropic.
The ionotropic receptor is the membrane protein that has an...

関連する実験動画