Department of Mathematics, Rutgers University, Piscataway, NJ, USA.
Methods Mol Biol. 2025;2870:51-62. doi: 10.1007/978-1-0716-4213-9_4.
This chapter addresses the following fundamental question: Do sequences of protein domains with sandwich architecture have common sequence characteristics even though they belong to different superfamilies and folds? The analysis was carried out in two stages: (1) determination of domain substructures shared by all sandwich proteins and (2) detection of common sequence characteristics within the substructures. Analysis of supersecondary structures in domains of proteins revealed two types of four-strand substructures that are common to sandwich proteins. At least one of these common substructures was found in proteins of 42 sandwich-like folds (per structural classification in the CATH database). A comparison of sequence fragments and residue-residue contacts constituting common substructures revealed specific distributions of hydrophobic residues in these chains. The shared sequences and structural characteristics can be conceptualized as the "grammatical rules of beta protein linguistics." Understanding the structural and sequence commonalities of sandwich proteins may prove useful for rational protein design.
具有三明治结构的蛋白质结构域序列即使属于不同的超家族和折叠，是否具有共同的序列特征？分析分两个阶段进行：（1）确定所有三明治蛋白共有的结构域亚结构；（2）检测亚结构内的共同序列特征。对蛋白质结构域中超二级结构的分析揭示了两种常见于三明治蛋白的四链亚结构。在 CATH 数据库的结构分类中，至少有 42 个类似三明治的折叠蛋白中发现了这两种常见的亚结构之一。比较构成常见亚结构的序列片段和残基-残基接触，揭示了这些链中疏水残基的特定分布。共享的序列和结构特征可以被概念化为“β 蛋白语言学的语法规则”。理解三明治蛋白的结构和序列共性可能对合理的蛋白质设计有用。
