Nucl Acids Res:中科大周丛照和陈宇星教授研究组共同提出一种新型
2016年3月2日，国际知名核酸研究期刊《Nucleic Acids Research》杂志在线发表中国科技大学周丛照和陈宇星教授研究组揭示的一种新型的蛋白质-DNA识别模式的研究成果，相关成果题为“Structures of an all-α protein running along the DNA major groove”。博士生余立艳以及博士后成望和周康为研究论文的共同第一作者，周丛照研究员和陈宇星教授为论文共同通讯作者。
蛋白与DNA之间的特异性识别在遗传信息的传递过程中具有非常重要的作用。尽管目前已有超过3000个蛋白质-DNA复合物结构被解析，但它们之间还有很多全新的识别模式尚未发现。利用X-射线晶体学解析的家蚕FMBP-1蛋白的DNA结合结构域 (简称BmSTPR)与靶DNA的复合物结构显示，该结构域的4个保守重复序列单元以串联 α螺旋的形式结合于DNA的大沟中，每个螺旋识别4个碱基对的DNA双链序列。进一步的生化实验和结构分析表明，BmSTPR通过形貌特异性(shape readout)而非碱基特异性(base readout)识别具有较高柔性和较宽大沟的富含AT的DNA序列。这种新型的DNA结合结构域广泛存在于各种动物中，暗示它们可能具有更加保守而重要的生物学功能。
相关阅读：EMBO Reports:中国科大周丛照和陈宇星研究组与清华王宏伟研究组合作揭示新型脊椎动物穿孔蛋白作用机制
图注：BmSTPR的晶体结构及DNA识别模式
原文链接：
Structures of an all-α protein running along the DNA major groove
原文摘要：
Despite over 3300 protein–DNA complex structures have been reported in the past decades, there remain some unknown recognition patterns between protein and target DNA. The silkgland-specific transcription factor FMBP-1 from the silkworm Bombyx mori contains a unique DNA-binding domain of four tandem STPRs, namely the score and three amino acid peptide repeats. Here we report three structures of this STPR domain (termed BmSTPR) in complex with DNA of various lengths. In the presence of target DNA, BmSTPR adopts a zig-zag structure of three or four tandem α-helices that run along the major groove of DNA. Structural analyses combined with binding assays indicate BmSTPR prefers the AT-rich sequences, with each α-helix covering a DNA sequence of 4 bp. The successive AT-rich DNAs adopt a wider major groove, which is in complementary in shape and size to the tandem α-helices of BmSTPR. Substitutions of DNA sequences and affinity comparison further prove thatBmSTPR recognizes the major groove mainly via shape readout. Multiple-sequence alignment suggests this unique DNA-binding pattern should be highly conserved for the STPR domain containing proteins which are widespread in animals. Together, our findings provide structural insights into the specific interactions between a novel DNA-binding protein and a unique deformed B-DNA.
作者：周丛照和陈宇星
