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Crystal structure of the BRPF2 PWWP domain in complex with DNA reveals a different binding mode than the HDGF family of PWWP domains
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms ( IF 4.7 ) Pub Date : 2021-02-06 , DOI: 10.1016/j.bbagrm.2021.194688
Mengmeng Zhang 1 , Ming Lei 2 , Su Qin 3 , Aiping Dong 4 , Ally Yang 5 , Yanjun Li 4 , Peter Loppnau 4 , Timothy R Hughes 5 , Jinrong Min 6 , Yanli Liu 1
Affiliation  

The PWWP domain was first identified in the HDGF protein family and named after the conserved Proline-Tryptophan-Tryptophan-Proline motif in WHSC1. The PWWP domain-containing proteins play important roles in different biological processes, such as DNA replication, transcription, DNA repair, pre-mRNA processing by recognizing methylated histone and dsDNA simultaneously. Recently, how the HDGF family of PWWP domains recognize histone H3K36me3-modified nucleosome has been reported. In order to better understand the interactions between the PWWP domain and dsDNA, we carried out family-wide characterization of dsDNA binding abilities of human PWWP domains. Our binding assays confirmed that PWWP domains bind to dsDNA without sequence selectivity. Our crystal structure of the BRPF2 PWWP domain in complex with a 12-mer dsDNA reveals that the PWWP domain interacts with dsDNA by binding to its major groove, instead of the minor groove observed in the HDGF family of PWWP domains. Our study indicates that PWWP domains could bind to dsDNA in different modes.



中文翻译:

与DNA复合的BRPF2 PWWP域的晶体结构揭示了与HDGF PWWP域家族不同的结合模式

PWWP域首先在HDGF蛋白家族中鉴定,并以WHSC1中保守的脯氨酸-色氨酸-色氨酸-脯氨酸基序命名。通过同时识别甲基化的组蛋白和dsDNA,含有PWWP域的蛋白质在不同的生物学过程中起着重要作用,例如DNA复制,转录,DNA修复,mRNA前加工。最近,已经报道了PWWP结构域的HDGF家族如何识别组蛋白H3K36me3修饰的核小体。为了更好地了解PWWP域与dsDNA之间的相互作用,我们对人PWWP域的dsDNA结合能力进行了全族范围的表征。我们的结合测定法证实PWWP结构域与dsDNA结合而没有序列选择性。我们的BRPF2 PWWP结构域与12-mer dsDNA形成复杂的晶体结构,揭示了PWWP结构域通过结合其主要凹槽而不是在HDGF系列PWWP结构域中观察到的次要凹槽与dsDNA相互作用。我们的研究表明,PWWP域可以以不同的模式与dsDNA结合。

更新日期:2021-02-15
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