DSSR-enabled G4 identification/annotation

Summary information and primary citation

PDB-id: 8x0s
Class: RNA
Method: X-ray (2.956 Å)
Summary: Crystal structure of r(g4c2)2
Reference: Geng Y, Liu C, Xu N, Suen MC, Miao H, Xie Y, Zhang B, Chen X, Song Y, Wang Z, Cai Q, Zhu G (2024): "Crystal structure of a tetrameric RNA G-quadruplex formed by hexanucleotide repeat expansions of C9orf72 in ALS/FTD." Nucleic Acids Res., 52, 7961-7970. doi: 10.1093/nar/gkae473.
Abstract: The abnormal GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause the fatal neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal dementia. The transcribed RNA HREs, short for r(G4C2)n, can form toxic RNA foci which sequestrate RNA binding proteins and impair RNA processing, ultimately leading to neurodegeneration. Here, we determined the crystal structure of r(G4C2)2, which folds into a parallel tetrameric G-quadruplex composed of two four-layer dimeric G-quadruplex via 5'-to-5' stacking in coordination with a K+ ion. Notably, the two C bases locate at 3'- end stack on the outer G-tetrad with the assistance of two additional K+ ions. The high-resolution structure reported here lays a foundation in understanding the mechanism of neurological toxicity of RNA HREs. Furthermore, the atomic details provide a structural basis for the development of potential therapeutic agents against the fatal neurodegenerative diseases ALS/FTD.
G4 notes: 8 G-tetrads, 1 G4 helix, 2 G4 stems, 1 G4 coaxial stack, UUUU, parallel, 4+0, coaxial interfaces: 5'/5'

Cartoon-block schematics in six views (download the tarball)

List of 8 G-tetrads

 1 glyco-bond=---- sugar=.-.- groove=---- planarity=0.151 type=planar -- nts=4 GGGG 1:A.G1,1:A.G7,2:A.G1,2:A.G7
 2 glyco-bond=---- sugar=3333 groove=---- planarity=0.167 type=other  -- nts=4 GGGG 1:A.G2,1:A.G8,2:A.G2,2:A.G8
 3 glyco-bond=---- sugar=---- groove=---- planarity=0.161 type=other  -- nts=4 GGGG 1:A.G3,1:A.G9,2:A.G3,2:A.G9
 4 glyco-bond=---- sugar=-3-3 groove=---- planarity=0.101 type=planar -- nts=4 GGGG 1:A.G4,1:A.G10,2:A.G4,2:A.G10
 5 glyco-bond=---- sugar=3-3- groove=---- planarity=0.164 type=other  -- nts=4 GGGG 1:B.G1,1:B.G7,2:B.G1,2:B.G7
 6 glyco-bond=---- sugar=3333 groove=---- planarity=0.187 type=other  -- nts=4 GGGG 1:B.G2,1:B.G8,2:B.G2,2:B.G8
 7 glyco-bond=---- sugar=---- groove=---- planarity=0.134 type=planar -- nts=4 GGGG 1:B.G3,1:B.G9,2:B.G3,2:B.G9
 8 glyco-bond=---- sugar=-3-3 groove=---- planarity=0.070 type=planar -- nts=4 GGGG 1:B.G4,1:B.G10,2:B.G4,2:B.G10

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, 8 G-tetrads, inter-molecular, with 2 stems

	1 glyco-bond=---- sugar=-3-3 groove=---- WC-->Major -- nts=4 GGGG 1:A.G4,1:A.G10,2:A.G4,2:A.G10 2 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.G3,1:A.G9,2:A.G3,2:A.G9 3 glyco-bond=---- sugar=3333 groove=---- WC-->Major -- nts=4 GGGG 1:A.G2,1:A.G8,2:A.G2,2:A.G8 4* glyco-bond=---- sugar=.-.- groove=---- WC-->Major -- nts=4 GGGG 1:A.G1,1:A.G7,2:A.G1,2:A.G7 5 glyco-bond=---- sugar=-3-3 groove=---- Major-->WC -- nts=4 GGGG 2:B.G7,2:B.G1,1:B.G7,1:B.G1 6 glyco-bond=---- sugar=3333 groove=---- Major-->WC -- nts=4 GGGG 2:B.G8,2:B.G2,1:B.G8,1:B.G2 7 glyco-bond=---- sugar=---- groove=---- Major-->WC -- nts=4 GGGG 2:B.G9,2:B.G3,1:B.G9,1:B.G3 8 glyco-bond=---- sugar=3-3- groove=---- Major-->WC -- nts=4 GGGG 2:B.G10,2:B.G4,1:B.G10,1:B.G4 step#1 mp(<<,backward) area=7.17 rise=3.23 twist=35.6 step#2 mp(<<,backward) area=15.26 rise=3.71 twist=20.8 step#3 mp(<<,backward) area=8.67 rise=3.28 twist=33.6 step#4 mm(<>,outward) area=8.74 rise=3.35 twist=25.9 step#5 pm(>>,forward) area=8.83 rise=3.28 twist=33.5 step#6 pm(>>,forward) area=15.71 rise=3.71 twist=20.3 step#7 pm(>>,forward) area=7.14 rise=3.23 twist=35.3 strand#1 RNA glyco-bond=-------- sugar=--3.-3-3 nts=8 GGGGGGGG 1:A.G4,1:A.G3,1:A.G2,1:A.G1,2:B.G7,2:B.G8,2:B.G9,2:B.G10 strand#2 RNA glyco-bond=-------- sugar=3-3-33-- nts=8 GGGGGGGG 1:A.G10,1:A.G9,1:A.G8,1:A.G7,2:B.G1,2:B.G2,2:B.G3,2:B.G4 strand#3 RNA glyco-bond=-------- sugar=--3.-3-3 nts=8 GGGGGGGG 2:A.G4,2:A.G3,2:A.G2,2:A.G1,1:B.G7,1:B.G8,1:B.G9,1:B.G10 strand#4 RNA glyco-bond=-------- sugar=3-3-33-- nts=8 GGGGGGGG 2:A.G10,2:A.G9,2:A.G8,2:A.G7,1:B.G1,1:B.G2,1:B.G3,1:B.G4 Download PDB file Interactive view in 3Dmol.js
7 stacking diagrams
	1 glyco-bond=---- sugar=-3-3 groove=---- WC-->Major -- nts=4 GGGG 1:A.G4,1:A.G10,2:A.G4,2:A.G10 2 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.G3,1:A.G9,2:A.G3,2:A.G9 step#1 mp(<<,backward) area=7.17 rise=3.23 twist=35.6 Download PDB file Interactive view in 3Dmol.js
	2 glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.G3,1:A.G9,2:A.G3,2:A.G9 3 glyco-bond=---- sugar=3333 groove=---- WC-->Major -- nts=4 GGGG 1:A.G2,1:A.G8,2:A.G2,2:A.G8 step#2 mp(<<,backward) area=15.26 rise=3.71 twist=20.8 Download PDB file Interactive view in 3Dmol.js
	3 glyco-bond=---- sugar=3333 groove=---- WC-->Major -- nts=4 GGGG 1:A.G2,1:A.G8,2:A.G2,2:A.G8 4* glyco-bond=---- sugar=.-.- groove=---- WC-->Major -- nts=4 GGGG 1:A.G1,1:A.G7,2:A.G1,2:A.G7 step#3 mp(<<,backward) area=8.67 rise=3.28 twist=33.6 Download PDB file Interactive view in 3Dmol.js
	4* glyco-bond=---- sugar=.-.- groove=---- WC-->Major -- nts=4 GGGG 1:A.G1,1:A.G7,2:A.G1,2:A.G7 5 glyco-bond=---- sugar=-3-3 groove=---- Major-->WC -- nts=4 GGGG 2:B.G7,2:B.G1,1:B.G7,1:B.G1 step#4 mm(<>,outward) area=8.74 rise=3.35 twist=25.9 Download PDB file Interactive view in 3Dmol.js
	5 glyco-bond=---- sugar=-3-3 groove=---- Major-->WC -- nts=4 GGGG 2:B.G7,2:B.G1,1:B.G7,1:B.G1 6 glyco-bond=---- sugar=3333 groove=---- Major-->WC -- nts=4 GGGG 2:B.G8,2:B.G2,1:B.G8,1:B.G2 step#5 pm(>>,forward) area=8.83 rise=3.28 twist=33.5 Download PDB file Interactive view in 3Dmol.js
	6 glyco-bond=---- sugar=3333 groove=---- Major-->WC -- nts=4 GGGG 2:B.G8,2:B.G2,1:B.G8,1:B.G2 7 glyco-bond=---- sugar=---- groove=---- Major-->WC -- nts=4 GGGG 2:B.G9,2:B.G3,1:B.G9,1:B.G3 step#6 pm(>>,forward) area=15.71 rise=3.71 twist=20.3 Download PDB file Interactive view in 3Dmol.js
	7 glyco-bond=---- sugar=---- groove=---- Major-->WC -- nts=4 GGGG 2:B.G9,2:B.G3,1:B.G9,1:B.G3 8 glyco-bond=---- sugar=3-3- groove=---- Major-->WC -- nts=4 GGGG 2:B.G10,2:B.G4,1:B.G10,1:B.G4 step#7 pm(>>,forward) area=7.14 rise=3.23 twist=35.3 Download PDB file Interactive view in 3Dmol.js

List of 2 G4-stems

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-tetrads, 2 loops, inter-molecular, UUUU, parallel, 4+0

 1  glyco-bond=---- sugar=.-.- groove=---- WC-->Major -- nts=4 GGGG 1:A.G1,1:A.G7,2:A.G1,2:A.G7
 2  glyco-bond=---- sugar=3333 groove=---- WC-->Major -- nts=4 GGGG 1:A.G2,1:A.G8,2:A.G2,2:A.G8
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:A.G3,1:A.G9,2:A.G3,2:A.G9
 4  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major -- nts=4 GGGG 1:A.G4,1:A.G10,2:A.G4,2:A.G10
  step#1  pm(>>,forward)  area=8.67  rise=3.28 twist=33.6
  step#2  pm(>>,forward)  area=15.26 rise=3.71 twist=20.8
  step#3  pm(>>,forward)  area=7.17  rise=3.23 twist=35.6
  strand#1  U RNA glyco-bond=---- sugar=.3-- nts=4 GGGG 1:A.G1,1:A.G2,1:A.G3,1:A.G4
  strand#2  U RNA glyco-bond=---- sugar=-3-3 nts=4 GGGG 1:A.G7,1:A.G8,1:A.G9,1:A.G10
  strand#3  U RNA glyco-bond=---- sugar=.3-- nts=4 GGGG 2:A.G1,2:A.G2,2:A.G3,2:A.G4
  strand#4  U RNA glyco-bond=---- sugar=-3-3 nts=4 GGGG 2:A.G7,2:A.G8,2:A.G9,2:A.G10
  loop#1 type=propeller strands=[#1,#2] nts=2 CC 1:A.C5,1:A.C6
  loop#2 type=propeller strands=[#3,#4] nts=2 CC 2:A.C5,2:A.C6

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Stem#2, 4 G-tetrads, 2 loops, inter-molecular, UUUU, parallel, 4+0

 1  glyco-bond=---- sugar=3-3- groove=---- WC-->Major -- nts=4 GGGG 1:B.G1,1:B.G7,2:B.G1,2:B.G7
 2  glyco-bond=---- sugar=3333 groove=---- WC-->Major -- nts=4 GGGG 1:B.G2,1:B.G8,2:B.G2,2:B.G8
 3  glyco-bond=---- sugar=---- groove=---- WC-->Major -- nts=4 GGGG 1:B.G3,1:B.G9,2:B.G3,2:B.G9
 4  glyco-bond=---- sugar=-3-3 groove=---- WC-->Major -- nts=4 GGGG 1:B.G4,1:B.G10,2:B.G4,2:B.G10
  step#1  pm(>>,forward)  area=8.83  rise=3.28 twist=33.5
  step#2  pm(>>,forward)  area=15.71 rise=3.71 twist=20.3
  step#3  pm(>>,forward)  area=7.14  rise=3.23 twist=35.3
  strand#1  U RNA glyco-bond=---- sugar=33-- nts=4 GGGG 1:B.G1,1:B.G2,1:B.G3,1:B.G4
  strand#2  U RNA glyco-bond=---- sugar=-3-3 nts=4 GGGG 1:B.G7,1:B.G8,1:B.G9,1:B.G10
  strand#3  U RNA glyco-bond=---- sugar=33-- nts=4 GGGG 2:B.G1,2:B.G2,2:B.G3,2:B.G4
  strand#4  U RNA glyco-bond=---- sugar=-3-3 nts=4 GGGG 2:B.G7,2:B.G8,2:B.G9,2:B.G10
  loop#1 type=propeller strands=[#1,#2] nts=2 CC 1:B.C5,1:B.C6
  loop#2 type=propeller strands=[#3,#4] nts=2 CC 2:B.C5,2:B.C6