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OB 折叠蛋白的结构、功能及治疗意义:从过去到现在的启示。

Structure, function and therapeutic implications of OB-fold proteins: A lesson from past to present.

出版信息

Brief Funct Genomics. 2020 Dec 4;19(5-6):377-389. doi: 10.1093/bfgp/elaa008.

DOI:10.1093/bfgp/elaa008
PMID:32393969
Abstract

Oligonucleotide/oligosaccharide-binding (OB)-fold proteins play essential roles in the regulation of genome and its correct transformation to the subsequent generation. To maintain the genomic stability, OB-fold proteins are implicated in various cellular processes including DNA replication, DNA repair, cell cycle regulation and maintenance of telomere. The diverse functional spectrums of OB-fold proteins are mainly due to their involvement in protein-DNA and protein-protein complexes. Mutations and consequential structural alteration in the OB-fold proteins often lead to severe diseases. Here, we have investigated the structure, function and mode of action of OB-fold proteins (RPA, BRCA2, DNA ligases and SSBs1/2) in cellular pathways and their relationship with diseases and their possible use in therapeutic intervention. Due to the crucial role of OB-fold proteins in regulating the key physiological process, a detailed structural understanding in the context of underlying mechanism of action and cellular complexity offers a new avenue to target OB-proteins for therapeutic intervention.

摘要

寡核苷酸/寡糖结合(OB)折叠蛋白在基因组的调控及其向后代的正确转化中发挥着重要作用。为了维持基因组的稳定性,OB 折叠蛋白参与了包括 DNA 复制、DNA 修复、细胞周期调控和端粒维持在内的各种细胞过程。OB 折叠蛋白的多样化功能谱主要归因于它们参与蛋白-DNA 和蛋白-蛋白复合物。OB 折叠蛋白的突变和随之而来的结构改变常常导致严重的疾病。在这里,我们研究了 OB 折叠蛋白(RPA、BRCA2、DNA 连接酶和 SSBs1/2)在细胞途径中的结构、功能和作用模式,以及它们与疾病的关系及其在治疗干预中的可能应用。由于 OB 折叠蛋白在调节关键生理过程中的关键作用,在作用机制和细胞复杂性的背景下进行详细的结构理解,为针对 OB 蛋白进行治疗干预提供了新的途径。

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