在自我组装的α/β中β-氨基酸预组织的结构后果: foldameric螺旋捆的基本研究
Joshua L Price1, W Seth Horne, Samuel H Gellman
1Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|August 20, 2010
概括
结晶了六个具有规律的骨干重复的新型α/β折叠体,揭示了稳定的四螺旋束结构. 这些折叠体表明β (3) ->循环替代物在螺旋束四元结构中一般适应良好.
科学领域:
- 生物化学和结构生物学.
- 类化学和折叠机设计.
背景情况:
- 阿尔法/β-折叠体通过结合阿尔法和β-氨基酸,提供独特的结构可能性.
- GCN4-pLIα-作为稳定的四螺旋束形成的模型.
- 之前的工作建立了一个alpha/beta-peptide foldamer (1) 与一个alphaalphabeta骨干,保留四度四度结构.
研究的目的:
- 研究在α/β-折膜中用循环β-残留物取代柔性β-α-氨基酸残留物的结构后果.
- 为了确定循环β-残余的结合是否保持了母折叠体中观察到的四螺旋束四元结构.
- 评估β (3) -->循环替换在实现稳定的折叠分子结构中的可通用性.
主要方法:
- 六个新的α/β-折膜的高分辨率晶体结构的确定.
- 基于GCN4-pLI支架与αααααααααααα骨干的α/ββββ折叠体的合成.
- 结晶结构与先前报告的折叠体相比较,包括那些具有β (3) ->循环残留物替代物.
主要成果:
- 所有六种新合成的α/β-折叠体结晶并采用未扭曲的四螺旋束四元结构.
- 阿尔法阿尔法贝塔脊柱的重复模式保持在晶体状态.
- 观察到的结构表明,β (3) -->循环替换通常与四螺旋束形成相兼容,与之前观察到的"杆"扭曲不同.
结论:
- 具有αααα骨干的α/ββ折叠体可以形成稳定,未扭曲的四螺旋束结构.
- 用循环β-残留物取代柔性β-α-氨基酸是一种可行的折叠体设计策略,通常保留四级结构.
- 虽然通常适应,但特定的β-环替代可能偶尔会导致结构不稳定.
相关概念视频
01:13Protein Organization
Overview
01:24Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
01:24Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
01:13Protein Organization
Overview
01:22Protein Folding
Overview
01:25Protein 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...