Torchy Morgan P, Hamiche Ali, Klaholz Bruno P
Department of Integrated Structural Biology, Centre for Integrative Biology (CBI), Institute of Genetics and of Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, Illkirch, France.
Cell Mol Life Sci. 2015 Jul;72(13):2491-507. doi: 10.1007/s00018-015-1880-8. Epub 2015 Mar 22.
Transcription regulation through chromatin compaction and decompaction is regulated through various chromatin-remodeling complexes such as nucleosome remodeling and histone deacetylation (NuRD) complex. NuRD is a 1 MDa multi-subunit protein complex which comprises many different subunits, among which histone deacetylases HDAC1/2, ATP-dependent remodeling enzymes CHD3/4, histone chaperones RbAp46/48, CpG-binding proteins MBD2/3, the GATAD2a (p66α) and/or GATAD2b (p66β) and specific DNA-binding proteins MTA1/2/3. Here, we review the currently known crystal and NMR structures of these subunits, the functional data and their relevance for biomedical research considering the implication of NuRD subunits in cancer and various other diseases. The complexity of this macromolecular assembly, and its poorly understood mode of interaction with the nucleosome, the repeating unit of chromatin, illustrate that this complex is a major challenge for structure-function relationship studies which will be tackled best by an integrated biology approach.
通过染色质压缩和解压缩进行的转录调控是由多种染色质重塑复合物调节的,如核小体重塑和组蛋白去乙酰化(NuRD)复合物。NuRD是一种1 MDa的多亚基蛋白质复合物,它包含许多不同的亚基,其中包括组蛋白去乙酰化酶HDAC1/2、ATP依赖性重塑酶CHD3/4、组蛋白伴侣RbAp46/48、CpG结合蛋白MBD2/3、GATAD2a(p66α)和/或GATAD2b(p66β)以及特异性DNA结合蛋白MTA1/2/3。在这里,我们回顾了这些亚基目前已知的晶体结构和核磁共振结构、功能数据以及它们在生物医学研究中的相关性,同时考虑到NuRD亚基在癌症和其他各种疾病中的作用。这种大分子组装的复杂性,以及其与染色质的重复单元核小体相互作用的方式尚不清楚,这表明该复合物对于结构-功能关系研究来说是一个重大挑战,而采用综合生物学方法将最能应对这一挑战。