孔形成ペプチドの効能と選択性の適合的微調整
Aram J Krauson1, O Morgan Hall1, Taylor Fuselier1
1Department of Biochemistry and Molecular Biology, Tulane University School of Medicine , New Orleans, Louisiana 70112, United States.
Journal of the American Chemical Society
|December 4, 2015
まとめ
膜浸透性ペプチドを修正すると,その機能が変化する. 単一のアミノ酸の変化により 哺乳類の細胞に対して無効だが 細菌に対して有効なペプチドが生成された.
科学分野:
- 生物化学
- 分子生物学
- バイオ物理学
背景:
- 膜浸透性ペプチドは細胞のプロセスに不可欠です.
- 配列-構造-機能関係を理解することは,ペプチドの活性を制御する鍵です.
- メリチンは,毛穴形成ペプチドの研究のモデルとして機能する.
研究 の 目的:
- メリチンの機能喪失変種を特定する
- ペプチドの活性と選択性を支配する配列構造機能関係を理解する.
- ペプチド機能を調節する戦略を探求する.
主な方法:
- メリチンを基にしたペプチドのスクリーニング
- ペプチドの活性を合成脂質ベジクルを使って測定し,含有量の漏れを測定する.
- ペプチド構成の変化 (アルファヘリクルス対ランダムコイル) と結合均衡の分析.
- 核細胞と細菌膜に対するペプチドの活性を調べる
主要な成果:
- 約3分の1のメリチンを基にしたペプチドは機能の喪失を示した.
- 非活性ペプチドでは,水害性からグリシンへの置換が一般的であった.
- レウシンからグリシンへの単一の変異は 機能の喪失を再現した
- 機能喪失ペプチドは哺乳類の細胞に対して無効でしたが,強力な殺菌活性を維持しました.
- アニオン性脂質によって活性が回復し,結合折り平衡の変化を示した.
結論:
- 螺旋状ペプチドのコンフォーメーションの微調整は,その活性と選択性を効果的に調節する.
- 結合-折りたたみバランスは,膜浸透性ペプチドの機能にとって重要である.
- 特定のペプチドの改変は,哺乳類の細胞に毒性を持たずに細菌滅菌活動などの選択的毒性につながる可能性があります.
さらに関連する動画
08:48Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
Published on: January 26, 2016
12.5K
11:44Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
Published on: October 2, 2018
13.3K
関連する概念動画
02:40Ligand Binding Sites
15.7K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.7K
01:25Protein Folding
12.5K
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...
12.5K
01:22Protein Folding
130.5K
Overview
130.5K
01:49Conserved Binding Sites
5.3K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.3K
01:09Multi-pass Transmembrane Proteins and β-barrels
6.8K
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...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
6.8K
01:26Bacterial Protein Maturation
701
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
701