Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada; Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Trends Biochem Sci. 2014 Nov;39(11):536-47. doi: 10.1016/j.tibs.2014.09.001. Epub 2014 Sep 29.
PWWP domain-containing proteins are often involved in chromatin-associated biological processes, such as transcriptional regulation and DNA repair, and recent studies have shown that the PWWP domain specifies chromatin localization. Mutations in the PWWP domain, a 100-150 amino acid motif, have been linked to various human diseases, emphasizing its importance. Structural studies reveal that PWWP domains possess a conserved aromatic cage for histone methyl-lysine recognition, and synergistically bind both histone and DNA, which contributes to their nucleosome-binding ability and chromatin localization. Furthermore, the PWWP domain often cooperates with other histone and DNA 'reader' or 'modifier' domains to evoke crosstalk between various epigenetic marks. Here, we discuss these recent advances in understanding the structure and function of the PWWP domain.
PWWP 结构域蛋白通常参与染色质相关的生物学过程,如转录调控和 DNA 修复,最近的研究表明 PWWP 结构域决定了染色质的定位。PWWP 结构域是一个由 100-150 个氨基酸组成的基序,其突变与多种人类疾病有关,这强调了它的重要性。结构研究表明,PWWP 结构域具有保守的芳香族笼,用于识别组蛋白甲基化赖氨酸,并且协同结合组蛋白和 DNA,这有助于它们的核小体结合能力和染色质定位。此外,PWWP 结构域通常与其他组蛋白和 DNA“读取器”或“修饰剂”结构域合作,引发各种表观遗传标记之间的串扰。在这里,我们讨论了这些关于 PWWP 结构域结构和功能的最新进展。