A systematic analysis of the beta hairpin motif in the Protein Data Bank
A systematic analysis of the beta hairpin motif in the Protein Data Bank
复制标题
DOI：
10.1002/pro.4020
复制
发表时间：
2021-01-07
期刊：
影响因子：
8
通讯作者：
Wilke, Claus O.
中科院分区：
文献类型：
--
作者：
DuPai, Cory D.;Davies, Bryan W.;Wilke, Claus O.
β发夹基序是一种普遍存在的蛋白质结构基序，可以在生命之树的分子中找到。这种基序在合成设计的蛋白质和肽中也很常见，以其稳定性和对广泛功能的适应性而闻名。在这里，我们系统地探测蛋白质数据库（PDB）中包含的所有49，000个独特的β发夹子结构，以揭示与稳定的β发夹结构相关的关键特征，包括氨基酸偏好和丰富的链间接触。我们发现，位置特异性氨基酸的偏好，而看到整个β发夹结构，是最明显的内转区域，在那里他们依赖于微妙的转动力学与转长度和二级结构。我们还建立了一套广泛的设计原则，如在特定位置包含天冬氨酸残基，并在选择转角区域的残基时仔细考虑所需的二级结构，这可以应用于产生编码含有β发夹结构的蛋白质或肽的文库。
The beta hairpin motif is a ubiquitous protein structural motif that can be found in molecules across the tree of life. This motif, which is also popular in synthetically designed proteins and peptides, is known for its stability and adaptability to broad functions. Here, we systematically probe all 49,000 unique beta hairpin substructures contained within the Protein Data Bank (PDB) to uncover key characteristics correlated with stable beta hairpin structure, including amino acid biases and enriched interstrand contacts. We find that position specific amino acid preferences, while seen throughout the beta hairpin structure, are most evident within the turn region, where they depend on subtle turn dynamics associated with turn length and secondary structure. We also establish a set of broad design principles, such as the inclusion of aspartic acid residues at a specific position and the careful consideration of desired secondary structure when selecting residues for the turn region, that can be applied to the generation of libraries encoding proteins or peptides containing beta hairpin structures.