Detailed DSSR results for the G-quadruplex: PDB entry 8psi

PDB id

8psi

Class

DNA

Method

NMR

Summary

G-quadruplex with a 1-nt v-shaped loop from a g-rich sequence with five g-runs

Reference

Vianney YM, Schroder N, Jana J, Chojetzki G, Weisz K (2023): "Showcasing Different G-Quadruplex Folds of a G-Rich Sequence: Between Rule-Based Prediction and Butterfly Effect." J.Am.Chem.Soc., 145, 22194-22205. doi: 10.1021/jacs.3c08336.

Abstract

In better understanding the interactions of G-quadruplexes in a cellular or noncellular environment, a reliable sequence-based prediction of their three-dimensional fold would be extremely useful, yet is often limited by their remarkable structural diversity. A G-rich sequence related to a promoter sequence of the PDGFR-β nuclease hypersensitivity element (NHE) comprises a G₃-G₃-G₂-G₄-G₃ pattern of five G-runs with two to four G residues. Although the predominant formation of three-layered canonical G-quadruplexes with uninterrupted G-columns can be expected, minimal base substitutions in a non-G-tract domain were shown to guide folding into either a basket-type antiparallel quadruplex, a parallel-stranded quadruplex with an interrupted G-column, a quadruplex with a V-shaped loop, or a (3+1) hybrid quadruplex. A 3D NMR structure for each of the different folds was determined. Supported by thermodynamic profiling on additional sequence variants, formed topologies were rationalized by the identification and assessment of specific critical interactions of loop and overhang residues, giving valuable insights into their contribution to favor a particular conformer. The variability of such tertiary interactions, together with only small differences in quadruplex free energies, emphasizes current limits for a reliable sequence-dependent prediction of favored topologies from sequences with multiple irregularly positioned G-tracts.

G4 notes

3 G-tetrads, 1 G4 helix, 1 G4 stem, 2(-LwX+Lw), (2+2), UDUD

 1 glyco-bond=s-s- sugar=---- groove=wnwn planarity=0.261 type=other  nts=4 GGGG A.DG1,A.DG7,A.DG20,A.DG14
 2 glyco-bond=-s-s sugar=---- groove=wnwn planarity=0.345 type=other  nts=4 GGGG A.DG2,A.DG6,A.DG21,A.DG13
 3 glyco-bond=---s sugar=---- groove=--wn planarity=0.160 type=planar nts=4 GGGG A.DG8,A.DG11,A.DG15,A.DG19

Helix#1, 3 G-tetrad layers, INTRA-molecular, with 1 stem

	1 glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG6,A.DG21,A.DG13 2 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG7,A.DG20,A.DG14 3 glyco-bond=--s- sugar=---- groove=-nw- Major-->WC nts=4 GGGG A.DG11,A.DG8,A.DG19,A.DG15 step#1 mm(<>,outward) area=13.68 rise=3.45 twist=19.0 step#2 pm(>>,forward) area=11.01 rise=3.41 twist=30.0 strand#1 DNA glyco-bond=-s- sugar=--- nts=3 GGG A.DG2,A.DG1,A.DG11 strand#2 DNA glyco-bond=s-- sugar=--- nts=3 GGG A.DG6,A.DG7,A.DG8 strand#3 DNA glyco-bond=-ss sugar=--- nts=3 GGG A.DG21,A.DG20,A.DG19 strand#4 DNA glyco-bond=s-- sugar=--- nts=3 GGG A.DG13,A.DG14,A.DG15 Download PDB file Interactive view in 3Dmol.js
2 stacking diagrams
	1 glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG6,A.DG21,A.DG13 2 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG7,A.DG20,A.DG14 step#1 mm(<>,outward) area=13.68 rise=3.45 twist=19.0 Download PDB file Interactive view in 3Dmol.js
	2 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG7,A.DG20,A.DG14 3 glyco-bond=--s- sugar=---- groove=-nw- Major-->WC nts=4 GGGG A.DG11,A.DG8,A.DG19,A.DG15 step#2 pm(>>,forward) area=11.01 rise=3.41 twist=30.0 Download PDB file Interactive view in 3Dmol.js

Stem#1, 2 G-tetrad layers, 3 loops, INTRA-molecular, UDUD, anti-parallel, 2(-LwX+Lw), (2+2)

1 glyco-bond=s-s- sugar=---- groove=wnwn Major-->WC nts=4 GGGG A.DG1,A.DG7,A.DG20,A.DG14 2 glyco-bond=-s-s sugar=---- groove=wnwn WC-->Major nts=4 GGGG A.DG2,A.DG6,A.DG21,A.DG13 step#1 mm(<>,outward) area=13.68 rise=3.45 twist=19.0 strand#1 U DNA glyco-bond=s- sugar=-- nts=2 GG A.DG1,A.DG2 strand#2 D DNA glyco-bond=-s sugar=-- nts=2 GG A.DG7,A.DG6 strand#3 U DNA glyco-bond=s- sugar=-- nts=2 GG A.DG20,A.DG21 strand#4 D DNA glyco-bond=-s sugar=-- nts=2 GG A.DG14,A.DG13 loop#1 type=lateral strands=[#1,#2] nts=3 GTA A.DG3,A.DT4,A.DA5 loop#2 type=diag-prop strands=[#2,#4] nts=5 GCGGC A.DG8,A.DC9,A.DG10,A.DG11,A.DC12 loop#3 type=lateral strands=[#4,#3] nts=5 GGCAG A.DG15,A.DG16,A.DC17,A.DA18,A.DG19 Download PDB file Interactive view in 3Dmol.js

 1 type=lateral   helix=#1 nts=4 GCGG A.DG8,A.DC9,A.DG10,A.DG11
 2 type=V-shaped  helix=#1 nts=5 GCGGG A.DG11,A.DC12,A.DG13,A.DG14,A.DG15
 3 type=lateral   helix=#1 nts=5 GGCAG A.DG15,A.DG16,A.DC17,A.DA18,A.DG19