Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD 20742, USA.
Nucleic Acids Res. 2019 Dec 16;47(22):11921-11930. doi: 10.1093/nar/gkz1008.
DNA can form many structures beyond the canonical Watson-Crick double helix. It is now clear that noncanonical structures are present in genomic DNA and have biological functions. G-rich G-quadruplexes and C-rich i-motifs are the most well-characterized noncanonical DNA motifs that have been detected in vivo with either proscribed or postulated biological roles. Because of their independent sequence requirements, these structures have largely been considered distinct types of quadruplexes. Here, we describe the crystal structure of the DNA oligonucleotide, d(CCAGGCTGCAA), that self-associates to form a quadruplex structure containing two central antiparallel G-tetrads and six i-motif C-C+ base pairs. Solution studies suggest a robust structural motif capable of assembling as a tetramer of individual strands or as a dimer when composed of tandem repeats. This hybrid structure highlights the growing structural diversity of DNA and suggests that biological systems may harbor many functionally important non-duplex structures.
DNA 可以形成多种结构,超越经典的沃森-克里克双螺旋。现在已经清楚的是,非经典结构存在于基因组 DNA 中,并具有生物学功能。富含 G 的 G-四联体和富含 C 的 i- 基序是最典型的非经典 DNA 基序,已经在体内检测到具有规定或推测的生物学作用。由于它们独立的序列要求,这些结构在很大程度上被认为是不同类型的四联体。在这里,我们描述了 DNA 寡核苷酸 d(CCAGGCTGCAA)的晶体结构,该寡核苷酸自身缔合形成包含两个中央反平行 G-四联体和六个 i- 基序 C-C+碱基对的四联体结构。溶液研究表明,该结构具有形成单体四聚体或串联重复时形成二聚体的稳健结构基序。这种混合结构突出了 DNA 不断增长的结构多样性,并表明生物系统可能包含许多具有重要功能的非双链结构。