Schwartz T, Behlke J, Lowenhaupt K, Heinemann U, Rich A
Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13125 Berlin, Germany.
Nat Struct Biol. 2001 Sep;8(9):761-5. doi: 10.1038/nsb0901-761.
The first crystal structure of a protein, the Z alpha high affinity binding domain of the RNA editing enzyme ADAR1, bound to left-handed Z-DNA was recently described. The essential set of residues determined from this structure to be critical for Z-DNA recognition was used to search the database for other proteins with the potential for Z-DNA binding. We found that the tumor-associated protein DLM-1 contains a domain with remarkable sequence similarities to Z alpha(ADAR). Here we report the crystal structure of this DLM-1 domain bound to left-handed Z-DNA at 1.85 A resolution. Comparison of Z-DNA binding by DLM-1 and ADAR1 reveals a common structure-specific recognition core within the binding domain. However, the domains differ in certain residues peripheral to the protein-DNA interface. These structures reveal a general mechanism of Z-DNA recognition, suggesting the existence of a family of winged-helix proteins sharing a common Z-DNA binding motif.
最近报道了与左手螺旋Z-DNA结合的RNA编辑酶ADAR1的Zα高亲和力结合结构域这一蛋白质的首个晶体结构。从该结构确定的对Z-DNA识别至关重要的一组关键残基，被用于在数据库中搜索其他具有Z-DNA结合潜力的蛋白质。我们发现肿瘤相关蛋白DLM-1包含一个与Zα（ADAR）具有显著序列相似性的结构域。在此我们报告该DLM-1结构域与左手螺旋Z-DNA结合的晶体结构，分辨率为1.85埃。对DLM-1和ADAR1与Z-DNA结合情况的比较揭示了结合结构域内一个共同的结构特异性识别核心。然而，这两个结构域在蛋白质-DNA界面外围的某些残基上存在差异。这些结构揭示了Z-DNA识别的一般机制，表明存在一个共享共同Z-DNA结合基序的翼状螺旋蛋白家族。
