Crystal structures of an HIV-1 integrase aptamer: formation of a water-mediated A•G•G•G•G pentad in an interlocked G-quadruplex

• Main Authors: Ngo, Khac Huy, Liew, Chong Wai, Lattmann, Simon, Winnerdy, Fernaldo Richtia, Phan, Anh Tuân
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Biological sciences; Science::Chemistry; G-Quadruplexes; Interlocked
• Online Access: https://hdl.handle.net/10356/158333
• Institution: Nanyang Technological University

93del is a 16-nucleotide G-quadruplex-forming aptamer which can inhibit the activity of the HIV-1 integrase enzyme at nanomolar concentration. Previous structural analyses of 93del using NMR spectroscopy have shown that the aptamer forms an interlocked G-quadruplex structure in K+ solution. Due to its exceptional stability and unique topology, 93del has been used in many different studies involving DNA G-quadruplexes, such as DNA aptamer and multimer design, as well as DNA fluorescence research. To gain further insights on the structure of this unique aptamer, we have determined several high-resolution crystal structures of 93del and its variants. While confirming the overall dimeric interlocked G-quadruplex folding topology previously determined by NMR, our results reveal important detailed structural information, particularly the formation of a water-mediated A•G•G•G•G pentad. These insights allow us to better understand the formation of various structural elements in G-quadruplexes and should be useful for designing and manipulating G-quadruplex scaffolds with desired properties.