Detailed DSSR results for the G-quadruplex: PDB entry 7zeo

PDB id

7zeo

Class

DNA

Method

NMR

Summary

Structure of a hybrid-type g-quadruplex with a snapback loop and an all-syn g-column (hybrid-1r)

Reference

Jana J, Vianney YM, Schroder N, Weisz K (2022): "Guiding the folding of G-quadruplexes through loop residue interactions." Nucleic Acids Res., 50, 7161-7175. doi: 10.1093/nar/gkac549.

Abstract

A G-rich sequence was designed to allow folding into either a stable parallel or hybrid-type topology. With the parent sequence featuring coexisting species, various related sequences with single and double mutations and with a shortened central propeller loop affected the topological equilibrium. Two simple modifications, likewise introduced separately to all sequences, were employed to lock folds into one of the topologies without noticeable structural alterations. The unique combination of sequence mutations, high-resolution NMR structural information, and the thermodynamic stability for both topological competitors identified critical loop residue interactions. In contrast to first loop residues, which are mostly disordered and exposed to solvent in both propeller and lateral loops bridging a narrow groove, the last loop residue in a lateral three-nucleotide loop is engaged in stabilizing stacking interactions. The propensity of single-nucleotide loops to favor all-parallel topologies by enforcing a propeller-like conformation of an additional longer loop is shown to result from their preference in linking two outer tetrads of the same tetrad polarity. Taken together, the present studies contribute to a better structural and thermodynamic understanding of delicate loop interactions in genomic and artificially designed quadruplexes, e.g. when employed as therapeutics or in other biotechnological applications.

G4 notes

3 G-tetrads, 1 G4 helix, 1 G4 stem, 2(+Ln+P+P), hybrid-1R(1+3), UDDD

 1 glyco-bond=s--- sugar=---- groove=w--n planarity=0.156 type=planar nts=4 gGGG A.L1J1,A.DG15,A.DG11,A.DG7
 2 glyco-bond=s--- sugar=---- groove=w--n planarity=0.170 type=other  nts=4 gGGG A.BGM2,A.DG14,A.DG10,A.DG6
 3 glyco-bond=---s sugar=---- groove=--wn planarity=0.276 type=bowl   nts=4 GGGG A.DG8,A.DG12,A.DG16,A.DG20

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

	1 glyco-bond=s--- sugar=---- groove=w--n Major-->WC nts=4 gGGG A.BGM2,A.DG14,A.DG10,A.DG6 2 glyco-bond=s--- sugar=---- groove=w--n Major-->WC nts=4 gGGG A.L1J1,A.DG15,A.DG11,A.DG7 3 glyco-bond=s--- sugar=---- groove=w--n Major-->WC nts=4 GGGG A.DG20,A.DG16,A.DG12,A.DG8 step#1 pm(>>,forward) area=14.59 rise=3.37 twist=24.8 step#2 pm(>>,forward) area=9.08 rise=3.45 twist=31.0 strand#1 DNA glyco-bond=sss sugar=--- nts=3 ggG A.BGM2,A.L1J1,A.DG20 strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG14,A.DG15,A.DG16 strand#3 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG10,A.DG11,A.DG12 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG A.DG6,A.DG7,A.DG8 Download PDB file Interactive view in 3Dmol.js
2 stacking diagrams
	1 glyco-bond=s--- sugar=---- groove=w--n Major-->WC nts=4 gGGG A.BGM2,A.DG14,A.DG10,A.DG6 2 glyco-bond=s--- sugar=---- groove=w--n Major-->WC nts=4 gGGG A.L1J1,A.DG15,A.DG11,A.DG7 step#1 pm(>>,forward) area=14.59 rise=3.37 twist=24.8 Download PDB file Interactive view in 3Dmol.js
	2 glyco-bond=s--- sugar=---- groove=w--n Major-->WC nts=4 gGGG A.L1J1,A.DG15,A.DG11,A.DG7 3 glyco-bond=s--- sugar=---- groove=w--n Major-->WC nts=4 GGGG A.DG20,A.DG16,A.DG12,A.DG8 step#2 pm(>>,forward) area=9.08 rise=3.45 twist=31.0 Download PDB file Interactive view in 3Dmol.js

Stem#1, 2 G-tetrad layers, 3 loops, INTRA-molecular, UDDD, hybrid-(mixed), 2(+Ln+P+P), hybrid-1R(1+3)

1 glyco-bond=s--- sugar=---- groove=w--n Major-->WC nts=4 gGGG A.L1J1,A.DG15,A.DG11,A.DG7 2 glyco-bond=s--- sugar=---- groove=w--n Major-->WC nts=4 gGGG A.BGM2,A.DG14,A.DG10,A.DG6 step#1 mp(<<,backward) area=14.59 rise=3.37 twist=24.8 strand#1 U --- glyco-bond=ss sugar=-- nts=2 gg A.L1J1,A.BGM2 strand#2 D DNA glyco-bond=-- sugar=-- nts=2 GG A.DG15,A.DG14 strand#3 D DNA glyco-bond=-- sugar=-- nts=2 GG A.DG11,A.DG10 strand#4 D DNA glyco-bond=-- sugar=-- nts=2 GG A.DG7,A.DG6 loop#1 type=lateral strands=[#1,#4] nts=3 CTA A.DC3,A.DT4,A.DA5 loop#2 type=propeller strands=[#4,#3] nts=2 GT A.DG8,A.DT9 loop#3 type=propeller strands=[#3,#2] nts=2 GT A.DG12,A.DT13 Download PDB file Interactive view in 3Dmol.js

 1 type=lateral   helix=#1 nts=5 GTCAG A.DG16,A.DT17,A.DC18,A.DA19,A.DG20