Shi Y, Berg J M
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Biochemistry. 1996 Mar 26;35(12):3845-8. doi: 10.1021/bi952384p.
Zinc finger domains of the Cys2His2 type are found in a large number of eukaryotic proteins. Various proteins containing these domains have been shown to bind specifically to DNA, RNA, and DNA-RNA hybrids. Structural studies of zinc finger protein-DNA complexes have revealed that the DNA molecules are underwound relative to canonical B-form. It has not been clear if zinc finger proteins recognize preexisting underwound conformations of DNA or if they induce such conformations upon binding. We report that the DNA binding domains of Sp1 and several designed zinc finger proteins unwind DNA upon binding. The extent of unwinding is consistent with that observed in zinc finger protein-DNA cocrystal structures. These DNA deformations may be important in determining overall binding affinities as well as influencing binding site preferences. Furthermore, changes in DNA conformation upon zinc finger protein binding may affect protein-protein interactions important for transcriptional regulation and other activities of zinc finger proteins.
Cys2His2型锌指结构域存在于大量真核生物蛋白质中。已证明各种含有这些结构域的蛋白质能特异性结合DNA、RNA以及DNA-RNA杂交体。锌指蛋白-DNA复合物的结构研究表明，相对于标准的B型，DNA分子发生了负超螺旋。目前尚不清楚锌指蛋白是识别预先存在的DNA负超螺旋构象，还是在结合时诱导出这种构象。我们报告，Sp1的DNA结合结构域和几种设计的锌指蛋白在结合时会使DNA解旋。解旋程度与锌指蛋白-DNA共晶体结构中观察到的一致。这些DNA变形可能在决定整体结合亲和力以及影响结合位点偏好方面很重要。此外，锌指蛋白结合后DNA构象的变化可能会影响对转录调控和锌指蛋白其他活性很重要的蛋白质-蛋白质相互作用。
