コイルの長さによる依存 <--> 膜環境におけるβシート移行
Matthias Meier1, Joachim Seelig
1Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Journal of the American Chemical Society
|January 1, 2008
まとめ
ペプチド鎖の長さは,重要なタンパク質集積構造であるベータシート形成に決定的な影響を及ぼします. より長いペプチド (n > 12) は,エントロピーによって駆動され,膜結合時に容易にβシートを形成します.
科学分野:
- バイオフィジックス 生物物理学
- タンパク質の折りたたみ
- 膜生物物理学 膜生物物理学
背景:
- ベータシートは,タンパク質集積物の主要な構造要素です.
- 膜結合時にベータシートに折り畳まれる設計ペプチドは,ランダムなコイルからベータ構造への移行熱力学を研究するためのモデルとして使用されます.
研究 の 目的:
- ランダムなコイルからベータシートへの移行にペプチド鎖の長さの影響を調査する.
- 膜相互作用中の設計ペプチド ((KIGAKI) n) でのベータシート形成の熱力学特性を解明する.
主な方法:
- 円形二重化 (CD) スペクトロスコーピーは,脂質膜の存在または欠如においてβシート含有量を測定するために使用されました.
- イソテルミックタイトレーション熱測定法 (ITC) は,小さなユニラメラー脂質ベジクルによるタイトレーション中に熱力学的結合パラメータを決定した.
- D-アミノ酸置換の類型が合成され,折り畳み反応の貢献を分離した.
主要な成果:
- ベータシート形成はペプチド鎖の長さに協力的依存を示し,n > 10-12のペプチドの有意な増加が観察されました.
- 膜結合はエントロピー主導のプロセスで,エンドサーミック結合エンタルピーが特徴です.
- n >=12のペプチドの場合,折りたたみ反応は熱力学的に好ましい (残留物あたりDeltaG°β ≈ -0.15 kcal/mol),エクソテルミック折りたたみ (残留物あたりΔH°β ≈ -0.2〜-0.6 kcal/mol) によって駆動され,不利なエントロピーによって相殺される.
結論:
- ペプチド鎖の長さは,ベータシート形成と膜結合の決定的な決定因子です.
- より長いペプチド (n >= 12) をベータシートに折りたたむことは,膜相互作用によって熱力学的に好ましい.
- 微妙な環境変化 (pH,温度) は,これらの移行の敏感性のために,集積とアミロイド線維の形成に大きく影響する可能性があります.
関連する概念動画
Multi-pass Transmembrane Proteins and β-barrels
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
Mechanisms of Membrane-bending
The living membranes are flexible due to their fluid mosaic nature; however, their bending into different shapes is an active process regulated by specific lipids and proteins. The membrane bending can be transient as seen in vesicles or stable for a long time as in microvilli. Cells regulate the size, location, and duration of the membrane curvature.
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Protein Diffusion in the Membrane
Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
Protein Folding
Overview
Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Membrane Fluidity
Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.Fatty acids tails of phospholipids can be either saturated or...


