Abstract
G-rich DNA sequences with tracts of three or more continuous guanines (G≥3) are known to have high propensity to adopt stable G-quadruplex (G4) structures. Bioinformatic analyses suggest high prevalence of G-rich sequences with short G-tracts (G≤2) in the human genome. However, due to limited structural studies, the folding principles of such sequences remain largely unexplored and hence poorly understood. Here, we present the solution NMR structure of a sequence named AT26 consisting of irregularly spaced G2 tracts and two isolated single guanines. The structure is a four-layered G4 featuring two bi-layered blocks, locked between themselves in an unprecedented fashion making it a stable scaffold. In addition to edgewise and propeller-type loops, AT26 also harbors two V-shaped loops: a 2-nt V-shaped loop spanning two G-tetrad layers and a 0-nt V-shaped loop spanning three G-tetrad layers, which are named as VS- and VR-loop respectively, based on their distinct structural features. The intra-lock motif can be a basis for extending the G-tetrad core and a very stable intra-locked G4 can be formed by a sequence with G-tracts of various lengths including several G2 tracts. Findings from this study will aid in understanding the folding of G4 topologies from sequences containing irregularly spaced multiple short G-tracts.
Highlights
Guanine-rich nucleic acids are known to have high propensity to fold into a non-canonical secondary structure, consisting of planar GGGG tetrads [1], termed Gquadruplex (G4) [2]
In the last three decades, G4 structures have attracted increasing attention, given that G-rich sequences are found in biologically relevant sites, such as telomeres, minisatellites, promoters, immunoglobulin class switch regions, replication initiation sites, mRNA untranslated regions (UTRs) and introns [3]
NMR and Circular dichroism (CD) spectroscopy of the AT26 sequence revealed the formation of a four-layered G4 structure
Summary
Guanine-rich nucleic acids are known to have high propensity to fold into a non-canonical secondary structure, consisting of planar GGGG tetrads [1], termed Gquadruplex (G4) [2]. In the last three decades, G4 structures have attracted increasing attention, given that G-rich sequences are found in biologically relevant sites, such as telomeres, minisatellites, promoters, immunoglobulin class switch regions, replication initiation sites, mRNA untranslated regions (UTRs) and introns [3]. G4 structures are highly polymorphic with regards to molecularity, relative strand arrangement, loop architecture and glycosidic bond conformation of the guanines [20,21,22]. The stability of G4s generally increases with the increasing number of stacked G-tetrads [23], but shares an inverse relationship with the loop lengths [24,25,26,27,28]. The majority of G4 structures reported in literature consists of three G-tetrad layers, with few reported structures containing either two layers, four layers or more [29]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
