具有封闭架构的α螺旋重复蛋白的合理设计
Lindsey Doyle1, Jazmine Hallinan1, Jill Bolduc1
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, Washington 98109, USA.
Nature
|December 18, 2015
概括
我们开发了计算方法, 从零开始使用几何原理来设计新的并联重复蛋白质架构. 这种方法成功地创造了在自然界中无法找到的独特,封闭的α-电磁体结构.
科学领域:
- 蛋白质工程
- 计算生物学
- 结构生物学
背景情况:
- 双重重复蛋白对于各种生物功能至关重要,包括结合,催化和材料组装.
- 它们的模块化性质允许各种架构和结合表面的快速演变.
- 现有的重复蛋白质结构表现出由重复单元几何决定的广泛折叠.
研究的目的:
- 开发和验证协同重复蛋白结构的新设计的计算方法.
- 创建基于纯粹的几何标准的新型蛋白质结构, 独立于自然蛋白质模板.
- 探索封闭的α-soluid重复蛋白 (α-toroids) 的设计空间.
主要方法:
- 由相互重复的几何约束驱动的计算设计策略的开发.
- 应用这些方法来设计具有相邻的N和C端的封闭的α-电磁体结构.
- 使用X射线晶体学验证设计的蛋白质结构.
主要成果:
- 成功地设计出一种新型的双重重复蛋白结构.
- 创建具有独特左侧螺旋结构的封闭的alpha-solenoid (alpha-toroid) 结构
- 通过X射线结晶学对几个设计的蛋白质结构进行实验验证.
- 独立于自然蛋白序列或结构模板的设计方法的证明.
结论:
- 基于几何原理的计算设计可以创建新的蛋白质折叠.
- 这种方法可以产生不同于自然界的双重重复蛋白结构.
- 设计的α-体结构代表了一种具有潜在应用的新型蛋白结构.
相关概念视频
Protein and Protein Structure
92.2K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
92.2K
Conservative Site-specific Recombination and Phase Variation
7.3K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
7.3K
Conserved 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
Protein Folding
130.4K
Overview
130.4K
Protein Organization
161.6K
Overview
161.6K
Protein Organization
10.0K
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....
10.0K


