Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs
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 struct...
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sg-ntu-dr.10356-1451562023-02-28T19:45:24Z Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs Maity, Arijit Winnerdy, Fernaldo Richtia Chang, Weili Denyse Chen, Gang Phan, Anh Tuân School of Physical and Mathematical Sciences School of Biological Sciences NTU Institute of Structural Biology Science::Biological sciences DNA Guanine 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. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Published version Singapore National Research Foundation Investigatorship [NRF-NRFI2017-09]; Singapore Ministry of Education Academic Research Fund Tier 2 [MOE2015-T2-1- 092]; Nanyang Technological University (NTU Singapore) grants (to A.T.P.). Funding for open access charge: Singapore National Research Foundation. 2020-12-14T07:50:27Z 2020-12-14T07:50:27Z 2020 Journal Article Maity, A., Winnerdy, F. R., Chang, W. D., Chen, G., & Phan, A. T. (2020). Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs. Nucleic Acids Research, 48(6), 3315-3327. doi:10.1093/nar/gkaa008 0305-1048 https://hdl.handle.net/10356/145156 10.1093/nar/gkaa008 32100003 6 48 3315 3327 en NRF-NRFI2017-09 MOE2015-T2-1- 092 Nucleic Acids Research © 2020 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. application/pdf |
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Science::Biological sciences DNA Guanine Maity, Arijit Winnerdy, Fernaldo Richtia Chang, Weili Denyse Chen, Gang Phan, Anh Tuân Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs |
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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. |
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School of Physical and Mathematical Sciences |
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School of Physical and Mathematical Sciences Maity, Arijit Winnerdy, Fernaldo Richtia Chang, Weili Denyse Chen, Gang Phan, Anh Tuân |
format |
Article |
author |
Maity, Arijit Winnerdy, Fernaldo Richtia Chang, Weili Denyse Chen, Gang Phan, Anh Tuân |
author_sort |
Maity, Arijit |
title |
Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs |
title_short |
Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs |
title_full |
Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs |
title_fullStr |
Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs |
title_full_unstemmed |
Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs |
title_sort |
intra-locked g-quadruplex structures formed by irregular dna g-rich motifs |
publishDate |
2020 |
url |
https://hdl.handle.net/10356/145156 |
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1759855231918669824 |