Bernstein Douglas A, Zittel Morgan C, Keck James L
Department of Biomolecular Chemistry, 550 Medical Science Center, 1300 University Avenue, University of Wisconsin Medical School, Madison, WI 53706-1532, USA.
EMBO J. 2003 Oct 1;22(19):4910-21. doi: 10.1093/emboj/cdg500.
RecQ family helicases catalyze critical genome maintenance reactions in bacterial and eukaryotic cells, playing key roles in several DNA metabolic processes. Mutations in recQ genes are linked to genome instability and human disease. To define the physical basis of RecQ enzyme function, we have determined a 1.8 A resolution crystal structure of the catalytic core of Escherichia coli RecQ in its unbound form and a 2.5 A resolution structure of the core bound to the ATP analog ATPgammaS. The RecQ core comprises four conserved subdomains; two of these combine to form its helicase region, while the others form unexpected Zn(2+)-binding and winged-helix motifs. The structures reveal the molecular basis of missense mutations that cause Bloom's syndrome, a human RecQ-associated disease. Finally, based on findings from the structures, we propose a mechanism for RecQ activity that could explain its functional coordination with topoisomerase III.
RecQ家族解旋酶催化细菌和真核细胞中关键的基因组维护反应，在多个DNA代谢过程中发挥关键作用。recQ基因的突变与基因组不稳定和人类疾病相关。为了确定RecQ酶功能的物理基础，我们测定了未结合形式的大肠杆菌RecQ催化核心的1.8埃分辨率晶体结构以及与ATP类似物ATPγS结合的核心的2.5埃分辨率结构。RecQ核心由四个保守亚结构域组成；其中两个结合形成其解旋酶区域，而其他亚结构域形成意想不到的锌离子结合和翼状螺旋基序。这些结构揭示了导致布卢姆综合征（一种与人类RecQ相关的疾病）的错义突变的分子基础。最后，基于结构研究结果，我们提出了一种RecQ活性机制，该机制可以解释其与拓扑异构酶III的功能协调。
