Summary information

PDB id
8c7b
Class
DNA
Method
NMR
Summary
Slow cation movements within tetramolecular g-quadruplex: vacant cation binding sites in addition to all syn g-quartet
Reference
Zalar M, Wang B, Plavec J, Sket P (2023): "Insight into Tetramolecular DNA G-Quadruplexes Associated with ALS and FTLD: Cation Interactions and Formation of Higher-Ordered Structure." Int J Mol Sci, 24. doi: 10.3390/ijms241713437.
Abstract
The G4C2 hexanucleotide repeat expansion in the c9orf72 gene is a major genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), with the formation of G-quadruplexes directly linked to the development of these diseases. Cations play a crucial role in the formation and structure of G-quadruplexes. In this study, we investigated the impact of biologically relevant potassium ions on G-quadruplex structures and utilized 15N-labeled ammonium cations as a substitute for K+ ions to gain further insights into cation binding and exchange dynamics. Through nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we demonstrate that the single d(G4C2) repeat, in the presence of 15NH4+ ions, adopts a tetramolecular G-quadruplex with an all-syn quartet at the 5'-end. The movement of 15NH4+ ions through the central channel of the G-quadruplex, as well as to the bulk solution, is governed by the vacant cation binding site, in addition to the all-syn quartet at the 5'-end. Furthermore, the addition of K+ ions to G-quadruplexes folded in the presence of 15NH4+ ions induces stacking of G-quadruplexes via their 5'-end G-quartets, leading to the formation of stable higher-ordered species.
G4 notes
4 G-tetrads, 1 G4 helix, 1 G4 stem, parallel(4+0), UUUU

Base-block schematics in six views

PyMOL session file PDB file View in 3Dmol.js

List of 4 G-tetrads

 1 glyco-bond=ssss sugar=---- groove=---- planarity=0.122 type=planar nts=4 GGGG A.DG1,D.DG19,C.DG13,B.DG7
 2 glyco-bond=---- sugar=---- groove=---- planarity=0.216 type=other  nts=4 GGGG A.DG2,D.DG20,C.DG14,B.DG8
 3 glyco-bond=---- sugar=---- groove=---- planarity=0.254 type=other  nts=4 GGGG A.DG3,D.DG21,C.DG15,B.DG9
 4 glyco-bond=---- sugar=---- groove=---- planarity=0.413 type=bowl   nts=4 GGGG A.DG4,D.DG22,C.DG16,B.DG10

List of 1 G4-helix

In DSSR, a G4-helix is defined by stacking interactions of G-tetrads, regardless of backbone connectivity, and may contain more than one G4-stem.

Helix#1, 4 G-tetrad layers, inter-molecular, with 1 stem

 1  glyco-bond=ssss sugar=---- groove=---- Major-->WC nts=4 GGGG A.DG1,D.DG19,C.DG13,B.DG7
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG2,D.DG20,C.DG14,B.DG8
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,D.DG21,C.DG15,B.DG9
 4  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,D.DG22,C.DG16,B.DG10
  step#1  mm(<>,outward)  area=18.68 rise=3.42 twist=14.4
  step#2  pm(>>,forward)  area=14.10 rise=3.24 twist=29.4
  step#3  pm(>>,forward)  area=8.95  rise=3.48 twist=30.5
  strand#1 DNA glyco-bond=s--- sugar=---- nts=4 GGGG A.DG1,A.DG2,A.DG3,A.DG4
  strand#2 DNA glyco-bond=s--- sugar=---- nts=4 GGGG D.DG19,D.DG20,D.DG21,D.DG22
  strand#3 DNA glyco-bond=s--- sugar=---- nts=4 GGGG C.DG13,C.DG14,C.DG15,C.DG16
  strand#4 DNA glyco-bond=s--- sugar=---- nts=4 GGGG B.DG7,B.DG8,B.DG9,B.DG10

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3 stacking diagrams 
 1  glyco-bond=ssss sugar=---- groove=---- Major-->WC nts=4 GGGG A.DG1,D.DG19,C.DG13,B.DG7
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG2,D.DG20,C.DG14,B.DG8
  step#1  mm(<>,outward)  area=18.68 rise=3.42 twist=14.4

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 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG2,D.DG20,C.DG14,B.DG8
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,D.DG21,C.DG15,B.DG9
  step#2  pm(>>,forward)  area=14.10 rise=3.24 twist=29.4

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 3  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,D.DG21,C.DG15,B.DG9
 4  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,D.DG22,C.DG16,B.DG10
  step#3  pm(>>,forward)  area=8.95  rise=3.48 twist=30.5

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List of 1 G4-stem

In DSSR, a G4-stem is defined as a G4-helix with backbone connectivity. Bulges are also allowed along each of the four strands.

Stem#1, 4 G-tetrad layers, 0 loops, inter-molecular, UUUU, parallel, parallel(4+0)

 1  glyco-bond=ssss sugar=---- groove=---- Major-->WC nts=4 GGGG A.DG1,D.DG19,C.DG13,B.DG7
 2  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG2,D.DG20,C.DG14,B.DG8
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG3,D.DG21,C.DG15,B.DG9
 4  glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.DG4,D.DG22,C.DG16,B.DG10
  step#1  mm(<>,outward)  area=18.68 rise=3.42 twist=14.4
  step#2  pm(>>,forward)  area=14.10 rise=3.24 twist=29.4
  step#3  pm(>>,forward)  area=8.95  rise=3.48 twist=30.5
  strand#1  U DNA glyco-bond=s--- sugar=---- nts=4 GGGG A.DG1,A.DG2,A.DG3,A.DG4
  strand#2  U DNA glyco-bond=s--- sugar=---- nts=4 GGGG D.DG19,D.DG20,D.DG21,D.DG22
  strand#3  U DNA glyco-bond=s--- sugar=---- nts=4 GGGG C.DG13,C.DG14,C.DG15,C.DG16
  strand#4  U DNA glyco-bond=s--- sugar=---- nts=4 GGGG B.DG7,B.DG8,B.DG9,B.DG10

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