Muthuswami R, Truman P A, Mesner L D, Hockensmith J W
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
J Biol Chem. 2000 Mar 17;275(11):7648-55. doi: 10.1074/jbc.275.11.7648.
Many members of the SWI2/SNF2 family of adenosine triphosphatases participate in the assembly/disassembly of multiprotein complexes involved in the DNA metabolic processes of transcription, recombination, repair, and chromatin remodeling. The DNA molecule serves as an essential effector or catalyst for most of the members of this particular class of proteins, and the structure of the DNA may be more important than the nucleotide sequence. Inspection of the DNA structure at sites where multiprotein complexes are assembled/disassembled for these various DNA metabolic processes reveals the presence of a common element: a double-stranded to single-stranded transition region. We now show that this DNA element is crucial for the ATP hydrolytic function of an SWI2/SNF2 family member: DNA-dependent ATPase A. We further demonstrate that a domain containing the seven helicase-related motifs that are common to the SWI2/SNF2 family of proteins mediates the interaction with the DNA, yielding specific DNA structural recognition. This study forms a primary step toward understanding the physico-biochemical nature of the interaction between a particular class of DNA-dependent ATPase and their DNA effectors. Furthermore, this study provides a foundation for development of mechanisms to specifically target this class of DNA-dependent ATPases.
三磷酸腺苷酶的SWI2/SNF2家族的许多成员参与了多蛋白复合物的组装/拆卸，这些复合物涉及转录、重组、修复和染色质重塑等DNA代谢过程。DNA分子是这类特殊蛋白质大多数成员的重要效应物或催化剂，DNA的结构可能比核苷酸序列更重要。在这些不同的DNA代谢过程中多蛋白复合物进行组装/拆卸的位点处检查DNA结构，发现存在一个共同元素：双链到单链的过渡区域。我们现在表明，这个DNA元素对于SWI2/SNF2家族成员——依赖DNA的ATP酶A的ATP水解功能至关重要。我们进一步证明，一个包含SWI2/SNF2家族蛋白质共有的七个解旋酶相关基序的结构域介导了与DNA的相互作用，产生特定的DNA结构识别。这项研究是理解一类特定的依赖DNA的ATP酶与其DNA效应物之间相互作用的物理生化性质的第一步。此外，这项研究为开发特异性靶向这类依赖DNA的ATP酶的机制奠定了基础。
