DSSR-enabled G4 identification/annotation: PDB entry 9cb5
Summary information and primary citation
- PDB-id
- 9cb5
- Class
- transcription-DNA
- Method
- X-ray (2.6 Å)
- Summary
- Crystal structure of nucleolin in complex with myc promoter g-quadruplex
- Reference
- Chen L, Dickerhoff J, Zheng KW, Erramilli S, Feng H, Wu G, Onel B, Chen Y, Wang KB, Carver M, Lin C, Sakai S, Wan J, Vinson C, Hurley L, Kossiakoff AA, Deng N, Bai Y, Noinaj N, Yang D (2025): "Structural basis for nucleolin recognition of MYC promoter G-quadruplex." Science, 388, eadr1752. doi: 10.1126/science.adr1752.
- Abstract
- The <i>MYC</i> oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than for nucleolin recognition element (NRE) RNA. Nucleolin's four RNA binding domains (RBDs) are essential for high-affinity MycG4 binding. We present the 2.6-angstrom crystal structure of the nucleolin-MycG4 complex, revealing a folded parallel three-tetrad G-quadruplex with two coordinating potassium ions (K<sub>+</sub>), interacting with RBD1, RBD2, and Linker12 through its 6-nucleotide (nt) central loop and 5' flanking region. RBD3 and RBD4 bind MycG4's 1-nt loops as demonstrated by nuclear magnetic resonance (NMR). Cleavage under targets and tagmentation sequencing confirmed nucleolin's binding to MycG4 in cells. Our results revealed a G4 conformation-based recognition by a regulating protein through multivalent interactions, suggesting that G4s are nucleolin's primary cellular substrates, indicating G4 epigenetic transcriptional regulation and helping G4-targeted drug discovery.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 3(-P-P-P)
Cartoon-block schematics in six views (download the tarball)
List of 3 G-tetrads
1 glyco-bond=---- sugar=--.- groove=---- planarity=0.196 type=other O+ nts=4 GGGG 1:F.DG3,1:F.DG7,1:F.DG16,1:F.DG20 2 glyco-bond=---- sugar=---- groove=---- planarity=0.238 type=other O+ nts=4 GGGG 1:F.DG4,1:F.DG8,1:F.DG17,1:F.DG21 3 glyco-bond=---- sugar=---- groove=---- planarity=0.370 type=bowl O+ nts=4 GGGG 1:F.DG5,1:F.DG9,1:F.DG18,1:F.DG22
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, 3 G-tetrads, INTRA-molecular, with 1 stem
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1 glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG3,1:F.DG7,1:F.DG16,1:F.DG20 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG4,1:F.DG8,1:F.DG17,1:F.DG21 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG5,1:F.DG9,1:F.DG18,1:F.DG22 step#1 pm(>>,forward) area=12.33 rise=3.38 twist=26.8 step#2 pm(>>,forward) area=9.60 rise=3.36 twist=29.5 strand#1 DNA glyco-bond=--- sugar=--- nts=3 GGG 1:F.DG3,1:F.DG4,1:F.DG5 strand#2 DNA glyco-bond=--- sugar=--- nts=3 GGG 1:F.DG7,1:F.DG8,1:F.DG9 strand#3 DNA glyco-bond=--- sugar=.-- nts=3 GGG 1:F.DG16,1:F.DG17,1:F.DG18 strand#4 DNA glyco-bond=--- sugar=--- nts=3 GGG 1:F.DG20,1:F.DG21,1:F.DG22 |
| 2 stacking diagrams | |
|
1 glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG3,1:F.DG7,1:F.DG16,1:F.DG20 |
|
2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG4,1:F.DG8,1:F.DG17,1:F.DG21 |
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, 3 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 3(-P-P-P)
|
1 glyco-bond=---- sugar=--.- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG3,1:F.DG7,1:F.DG16,1:F.DG20 2 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG4,1:F.DG8,1:F.DG17,1:F.DG21 3 glyco-bond=---- sugar=---- groove=---- WC-->Major O+ nts=4 GGGG 1:F.DG5,1:F.DG9,1:F.DG18,1:F.DG22 step#1 pm(>>,forward) area=12.33 rise=3.38 twist=26.8 step#2 pm(>>,forward) area=9.60 rise=3.36 twist=29.5 strand#1 U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:F.DG3,1:F.DG4,1:F.DG5 strand#2 U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:F.DG7,1:F.DG8,1:F.DG9 strand#3 U DNA glyco-bond=--- sugar=.-- nts=3 GGG 1:F.DG16,1:F.DG17,1:F.DG18 strand#4 U DNA glyco-bond=--- sugar=--- nts=3 GGG 1:F.DG20,1:F.DG21,1:F.DG22 loop#1 type=propeller strands=[#1,#2] nts=1 A 1:F.DA6 loop#2 type=propeller strands=[#2,#3] nts=6 TTTTTA 1:F.DT10,1:F.DT11,1:F.DT12,1:F.DT13,1:F.DT14,1:F.DA15 loop#3 type=propeller strands=[#3,#4] nts=1 T 1:F.DT19 |