Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
Department of Integrative Biology, University of Texas at Austin, Austin, Texas, USA.
Protein Sci. 2021 Mar;30(3):613-623. doi: 10.1002/pro.4020. Epub 2021 Jan 7.
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.
β发夹模体是一种普遍存在的蛋白质结构模体，可以在生命之树中的各种分子中找到。这种模体在合成设计的蛋白质和肽中也很流行，以其稳定性和对广泛功能的适应性而闻名。在这里，我们系统地探测了蛋白质数据库（PDB）中包含的所有 49000 个独特的β发夹亚结构，以揭示与稳定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，虽然在整个β发夹结构中都可以看到位置特异性氨基酸偏好，但在转角区域最为明显，它们取决于与转角长度和二级结构相关的微妙转角动力学。我们还建立了一套广泛的设计原则，例如在特定位置包含天冬氨酸残基，以及在选择转角区域的残基时仔细考虑所需的二级结构，这些原则可以应用于生成包含β发夹结构的蛋白质或肽文库。
