2014年5月8日，中科院生物物理所許瑞明研究組、朱冰研究組和華東師範大學翁傑敏研究組合作在Molecular Cell雜誌發表了題目為"Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2"的研究成果，該研究報導了5-羥甲基化胞嘧啶（5hmC）被UHRF2-SRA結構域特異識別的分子機制，首次證實了UHRF2蛋白作為5hmC特異識別蛋白的存在（5hmC specific reader）。
研究團隊通過解析UHRF2-SRA與含有5hmC、5mC和C的多種DNA複合物的晶體結構分析不同修飾的胞嘧啶在SRA結合口袋中的差異，並揭示了5hmC的羥基與Thr508形成的一個多餘氫鍵，是UHRF2-SRA對5hmC具有更強親和力的原因。研究團隊比較UHRF2-SRA-5hmC與UHRF1-SRA-5mC的結構後發現兩個胺基酸的差異是UHRF2-SRA特異識別5hmC的結構基礎。相對於UHRF1-SRA特異識別半甲基化的DNA（hemi-modified），UHRF2-SRA更偏好結合雙邊修飾的DNA（fully-modified），研究團隊進一步通過一種雙邊鹼基都翻轉出來的複合物結構闡明了UHRF2 的NKR loop區域對其雙邊修飾選擇性的影響。這些結果對於更加深入地理解5hmC的功能起著重要的推動作用。(生物谷Bioon.com)
生物谷推薦的英文摘要：
Molecular Cell doi：10.1016/j.molcel
Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2
Ting Zhou, Jun Xiong, Mingzhu Wang, Na Yang, Jiemin Wong, Bing Zhu, Rui-Ming Xu
Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.