リンガンドの認識とグルコーストランスポーターの分子基礎
Dong Deng1,2,3, Pengcheng Sun1,2,3, Chuangye Yan1,2,3
1State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.
Nature
|July 16, 2015
まとめ
研究者は,ヒトのグルコーストランスポーター3 (GLUT3) がグルコースとマルトースに結合する高解像度構造を決定した. これは,トランスポーターに関する重要な洞察を明らかにします.
科学分野:
- 生物化学
- 構造生物学
- 膜輸送
背景:
- メジャーファシリテーター・スーパーファミリー (MFS) のグルコーストランスポーターは,ヒトのGLUT1−4と同様に,溶液輸送に不可欠である.
- その構造とメカニズムを理解することは 代謝研究にとって不可欠です
研究 の 目的:
- D-グルコースとの複合体におけるヒトGLUT3の高解像度構造を解明する.
- 構造分析を用いてGLUT3の構造状態と結合を調査する.
主な方法:
- 脂質立方相結晶化について
- マイクロフォーカスのX線散射
- 高解像度で3つの異なるGLUT3構造の決定 (1.5 Å, 2.6 Å, 2.4 Å).
主要な成果:
- ヒトのGLUT3の構造を1.5 Åの解像度でD-グルコースで外側に隠した状態で決定した.
- 外側開いた状態と外側閉じた状態でGLUT3の構造が得られる.
- カーボキシ末端領域の極性残基をプライマリリガンドコーディネーターとして特定した.
- 形状の変化の際の 細胞膜の重組を観察した.
結論:
- C端領域は,GLUTにおける主要な基板結合部位として機能する.
- GLUT3とGLUT1の構造を比較することで,GLUTの交替アクセスメカニズムについての洞察を得ました.
- GLUT のメカニズム的理解と構造主導のリガンド設計のための枠組みを提供します.
関連する概念動画
Glucose Transporters
28.4K
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
28.4K
Membrane Proteins
31.5K
Plasma membranes have integral transmembrane proteins involved in facilitated transport. These proteins are collectively referred to as transport proteins, and they function as either channels for the material or as carriers themselves. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids and a hydrophilic channel through their core that provides a hydrated opening for solutes to pass through the membrane layers. Passage through the channel allows...
31.5K
Glucose Absorption Into the Small Intestine
37.5K
Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...
37.5K
Secondary Active Transport
13.8K
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...
13.8K
Secondary Active Transport
141.4K
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...
141.4K
The Significance of Membrane Transport
44.7K
The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
44.7K


