アシンクロンサブユニットトランジション プライムアセチルコリン受容体の活性化
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PubMedで要約を見る
まとめ
この要約は機械生成です。筋肉のニコチンアセチルコリン受容体に結合するアゴニストは,中間構造を安定させ,連続的な活性化メカニズムを明らかにする. この発見は シナプス通信に不可欠な これらの受容体が 不活性状態から活性状態への移行を 説明しています
科学分野
- 神経科学
- 構造生物学
- 生物化学
背景
- ポストシナプス受容体は化学信号を電気反応に変換することでシナプス通信を媒介する.
- リガンドゲートイオンチャネルは,アゴニスト結合時に構造変化を起こし,チャネル開きとポストシナプス信号伝達に影響を与えます.
研究 の 目的
- 筋肉型ニコチンアセチルコリン受容体の活性化に伴う構造的メカニズムを解明する.
- 無結合,単結合,二結合状態の受容体の構造を決定する.
主な方法
- 筋肉型のニコチンアセチルコリン受容体の高解像度構造的決定
- 構造的な状態と機能的な活動を相関させるためのシングルチャネル記録.
主要な成果
- アゴニストが単一の部位に結合すると,一方のサブユニットが活性型構造を採用し,もう一方のサブユニットが非活性化します.
- 中間構造が特定され,受容体の活性化中に非同期的なサブユニット移行が明らかになった.
結論
- 筋肉型のニコチンアセチルコリン受容体の活性化は,非同期的なサブユニット移行を含む連続的なメカニズムを経由する.
- このメカニズムは,ペンタメリクリガンドゲートイオンチャネルのより広範なスーパーファミリーの機能を理解するための意味を持つ.
関連する概念動画
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...