State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai 200433, China.
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai 200433, China.
Nucleic Acids Res. 2018 Nov 30;46(21):11627-11638. doi: 10.1093/nar/gky902.
DNA can form diverse structures, which predefine their physiological functions. Besides duplexes that carry the genetic information, quadruplexes are the most well-studied DNA structures. In addition to their important roles in recombination, replication, transcription and translation, DNA quadruplexes have also been applied as diagnostic aptamers and antidisease therapeutics. Herein we further expand the sequence and structure complexity of DNA quadruplex by presenting a high-resolution crystal structure of DNA1 (5'-AGAGAGATGGGTGCGTT-3'). This is the first quadruplex structure that contains all the internal A-, G-, C-, T-tetrads, A:T:A:T tetrads and bulged nucleotides in one single structure; as revealed by site-specific mutagenesis and biophysical studies, the central ATGGG motif plays important role in the quadruplex formation. Interestingly, our structure also provides great new insights into cation recognition, including the first-time reported Pb2+, by tetrad structures.
DNA 可以形成多种结构，这些结构预先定义了它们的生理功能。除了携带遗传信息的双链体外，四链体是研究最多的 DNA 结构。除了在重组、复制、转录和翻译中发挥重要作用外，DNA 四链体还被用作诊断适体和抗疾病治疗剂。在此，我们通过展示 DNA1（5'-AGAGAGATGGGTGCGTT-3'）的高分辨率晶体结构，进一步扩展了 DNA 四链体的序列和结构复杂性。这是第一个包含单个结构中所有内部 A-、G-、C-、T-四联体、A:T:A:T 四联体和凸起核苷酸的四链体结构；通过定点突变和生物物理研究表明，中央 ATGGG 基序在四链体形成中起着重要作用。有趣的是，我们的结构还为阳离子识别提供了新的见解，包括首次报道的四联体结构中的 Pb2+。
