グルタミン酸-GABAアンチポーターの構造とメカニズム
Dan Ma1, Peilong Lu, Chuangye Yan
1Ministry of Education Protein Science Laboratory, Center for Structural Biology, Tsinghua University, Beijing 100084, China.
Nature
|March 13, 2012
まとめ
エシェリキア大腸菌は,グルタミン酸とGABAを交換することによって,胃酸を生き残るためにGadCトランスポーターを使用します. この研究は,GadCを明らかにしています.
科学分野:
- 微生物学 微生物学とは
- 構造生物学 構造生物学とは
- バイオケミストリー バイオケミストリー
背景:
- 食物媒介性出血性Escherichia coli菌株 (例えば,O157:H7) は,胃の低pH (~2) に生存するために,酸耐性システム (ARs) を有しています.
- AR2システムは,L-グルタミン酸 (Glu) のデカルボキシル化と,GadCトランスポーターによって媒介されるγ-アミノバター酸 (GABA) /Glu交換を伴う.
- GadCは,アミノ酸ポリアミン-オルガノケーションスーパーファミリーに属しますが,その機能的メカニズムは十分に理解されていません.
研究 の 目的:
- E. coli GadCトランスポーターの機能的メカニズムと構造的基礎を解明する.
- GadC.のpHに依存する輸送活動を調査する.
- GadCの構造を決定し,主要残留物と輸送経路を特定する.
主な方法:
- 異なるpH条件下でのGadC活性を評価するために,インビトロのプロテオリポソームベースの輸送測定法.
- E. coli GadC.の3.1 Å解像度構造を決定するためのX線結晶学.
- 重要な輸送残留物と経路を特定するための構造的および生化学的分析.
主要な成果:
- GadCはpHに依存する輸送活動を示し,酸性条件 (pH <6.5) の下でしか機能しない.
- 結晶構造は,閉じた状態のGadCを明らかにし,12のトランスメブランセグメントと,プラグとして機能するカーボキシ端末ドメインを有していた.
- 重要な輸送残留物と輸送経路が特定され,螺旋束の回転を含むメカニズムが示唆されました.
結論:
- GadCの機能は,胃内のE. coliの生存に不可欠な酸性環境によって厳格に規制されています.
- 決定された構造は,GadC.の閉じた状態とメカニズムについての洞察を提供します.
- GadCおよび関連するアミノ酸アンチポーターについて,固体回転を含む保存された輸送機構が提案されています.
さらに関連する動画
07:51Inhibitory Synapse Formation in a Co-culture Model Incorporating GABAergic Medium Spiny Neurons and HEK293 Cells Stably Expressing GABAA Receptors
Published on: November 14, 2014
07:16Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
関連する概念動画
01:55Secondary Active Transport
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
01:32Secondary Active Transport
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
01:19Ligand-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...
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...
01:19Ligand-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...
01:18Antiepileptic Drugs: GABAergic Pathway Potentiators
γ-aminobutyric acid or GABA, plays a pivotal role as an inhibitory neurotransmitter in the brain. GABA pathway potentiators, also known as GABAergic drugs, are a class of pharmaceutical agents designed to enhance the functioning of the GABAergic system. These medications primarily treat epilepsy, a neurological disorder characterized by recurrent seizures.
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for their...
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for their...