Implications of disease-related mutations at protein–protein interfaces. (February 2022)

• Record Type: Journal Article
• Authors: Xiong, Dapeng; Lee, Dongjin; Li, Le; Zhao, Qiuye; Yu, Haiyuan
• Is Part Of: Current opinion in structural biology. Volume 72(2022)
• Page Start: 219
• Page End: 225
• Publication Date: 2022-02
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2021.11.012
• Languages: English
• ISSNs: 0959-440X

Abstract

Abstract: Protein–protein interfaces have been attracting great attention owing to their critical roles in protein–protein interactions and the fact that human disease-related mutations are generally enriched in them. Recently, substantial research progress has been made in this field, which has significantly promoted the understanding and treatment of various human diseases. For example, many studies have discovered the properties of disease-related mutations. Besides, as more large-scale experimental data become available, various computational approaches have been proposed to advance our understanding of disease mutations from the data. Here, we overview recent advances in characteristics of disease-related mutations at protein–protein interfaces, mutation effects on protein interactions, and investigation of mutations on specific diseases. Highlights: Disease-related mutations preferentially localize to protein–protein interfaces. Mutations, in general, destabilize protein–protein interactions and protein structures. Deep learning shows great advantages and potentials in mutation effect prediction. Pathogenic mutations may lead to different diseases by disrupting or changing the binding affinity.