Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, United States.
J Mol Biol. 2021 Feb 19;433(4):166788. doi: 10.1016/j.jmb.2020.166788. Epub 2020 Dec 31.
The Rossmann-like fold is the most prevalent and diversified doubly-wound superfold of ancient evolutionary origin. Rossmann-like domains are present in a variety of metabolic enzymes and are capable of binding diverse ligands. Discerning evolutionary relationships among these domains is challenging because of their diverse functions and ancient origin. We defined a minimal Rossmann-like structural motif (RLM), identified RLM-containing domains among known 3D structures (20%) and classified them according to their homologous relationships. New classifications were incorporated into our Evolutionary Classification of protein Domains (ECOD) database. We defined 156 homology groups (H-groups), which were further clustered into 123 possible homology groups (X-groups). Our analysis revealed that RLM-containing proteins constitute approximately 15% of the human proteome. We found that disease-causing mutations are more frequent within RLM domains than within non-RLM domains of these proteins, highlighting the importance of RLM-containing proteins for human health.
罗斯曼样折叠是最普遍和多样化的双重扭曲超折叠，具有古老的进化起源。罗斯曼样结构域存在于各种代谢酶中，能够结合多种配体。由于它们的功能多样和起源古老，识别这些结构域之间的进化关系具有挑战性。我们定义了一个最小的罗斯曼样结构基序 (RLM)，在已知的 3D 结构中识别出含有 RLM 的结构域（占 20%），并根据它们的同源关系进行分类。新的分类被纳入我们的蛋白质结构域进化分类 (ECOD) 数据库。我们定义了 156 个同源组 (H-组)，并进一步聚类为 123 个可能的同源组 (X-组)。我们的分析表明，含有 RLM 的蛋白质约占人类蛋白质组的 15%。我们发现，致病突变在这些蛋白质的 RLM 结构域内比在非 RLM 结构域内更为频繁，这突出了含有 RLM 的蛋白质对人类健康的重要性。
