Structural Biology Laboratory, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Structure. 2010 Feb 10;18(2):177-87. doi: 10.1016/j.str.2009.12.011.
The RecQ family of DNA helicases including WRN (Werner syndrome protein) and BLM (Bloom syndrome protein) protects the genome against deleterious changes. Here we report the cocrystal structure of the RecQ C-terminal (RQC) domain of human WRN bound to a DNA duplex. In the complex, the RQC domain specifically interacted with a blunt end of the duplex and, surprisingly, unpaired a Watson-Crick base pair in the absence of an ATPase domain. The beta wing, an extended hairpin motif that is characteristic of winged-helix motifs, was used as a "separating knife" to wedge between the first and second base pairs, whereas the recognition helix, a principal component of helix-turn-helix motifs that are usually embedded within DNA grooves, was unprecedentedly excluded from the interaction. Our results demonstrate a function of the winged-helix motif central to the helicase reaction, establishing the first structural paradigm concerning the DNA structure-specific activities of the RecQ helicases.
RecQ 家族 DNA 解旋酶包括 WRN（早老综合征蛋白）和 BLM（布卢姆综合征蛋白），可保护基因组免受有害变化的影响。在这里，我们报告了人 WRN 的 RecQ C 端（RQC）结构域与 DNA 双链复合物的晶体结构。在该复合物中，RQC 结构域特异性地与双链体的平末端相互作用，并且令人惊讶的是，在没有 ATP 酶结构域的情况下，非配对 Watson-Crick 碱基对。β 翼，一个延伸的发夹模体，是翼螺旋模体的特征，被用作“分离刀”，楔入第一和第二碱基对之间，而识别螺旋，是通常嵌入 DNA 凹槽内的螺旋-转角-螺旋模体的主要成分，以前从未被排除在相互作用之外。我们的结果证明了该螺旋酶反应的中心翼螺旋模体的功能，确立了第一个关于 RecQ 螺旋酶的 DNA 结构特异性活性的结构范例。
