控制质折叠与酸化氨基酸和三之间的排斥性相互作用
Alexander J Riemen1, Marcey L Waters
1Department of Chemistry, CB 3290, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Journal of the American Chemical Society
|September 12, 2009
概括
氨基酸的酸化,如氨酸,氨酸和氨酸,由于排斥性相互作用,使β-hairpin结构不稳定1.0kcal/mol. 这项研究揭示了酸化影响蛋白质功能的新方法.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 蛋白质化学 蛋白质化学
背景情况:
- 蛋白质酸化是调节蛋白质功能的关键翻译后修饰.
- 酸化的结构后果,特别是它对和蛋白质稳定性的影响,尚未完全理解.
- 贝塔毛刺是蛋白质中常见的结构图案.
研究的目的:
- 为了研究化常见的氨基酸残留物 (氨酸,氨酸,氨酸,氨酸) 对β-hairpin结构的影响.
- 阐明酸化影响β-hairpin稳定性的机制.
- 为了比较酸化的破坏稳定作用与负电荷残留物 (谷氨酸) 的破坏稳定作用.
主要方法:
- 设计和合成一个含有酸化氨酸,氨酸和氨酸残留物的β-hairpin.
- 差分扫描热度计或循环二元法,以评估发针稳定性.
- 双重突变周期分析和pH依赖性研究,以探测相互作用机制.
主要成果:
- 酸化氨酸,氨酸或氨酸使β-hairpin结构不稳定了大约1.0kcal/mol.
- 这种不稳定是独立于特定的酸化残留物.
- 由谷氨酸造成的不稳定性明显较小 (~0.3 kcal/mol),研究表明排斥性相互作用是原因.
结论:
- 酸化对β-hairpin结构引入了显著的破坏稳定力,主要是通过排斥性相互作用.
- 这一发现提出了一个新的机制,酸化可以调节蛋白质结构,从而调节蛋白质功能.
- 通过酸化破坏稳定的程度大于类似充电的残留物,如谷氨酸.
相关概念视频
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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.
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Protein Folding
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Protein Organization
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Protein 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.
Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
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