DSSR-enabled G4 identification/annotation: PDB entry 5de8
Summary information and primary citation
- PDB-id
- 5de8
- Class
- RNA binding protein-RNA
- Method
- X-ray (3.1 Å)
- Summary
- Crystal structure of the complex between human fmrp rgg motif and g-quadruplex RNA, iridium hexammine bound form.
- Reference
- Vasilyev N, Polonskaia A, Darnell JC, Darnell RB, Patel DJ, Serganov A (2015): "Crystal structure reveals specific recognition of a G-quadruplex RNA by a beta-turn in the RGG motif of FMRP." Proc.Natl.Acad.Sci.USA, 112, E5391-E5400. doi: 10.1073/pnas.1515737112.
- Abstract
- Fragile X Mental Retardation Protein (FMRP) is a regulatory RNA binding protein that plays a central role in the development of several human disorders including Fragile X Syndrome (FXS) and autism. FMRP uses an arginine-glycine-rich (RGG) motif for specific interactions with guanine (G)-quadruplexes, mRNA elements implicated in the disease-associated regulation of specific mRNAs. Here we report the 2.8-Å crystal structure of the complex between the human FMRP RGG peptide bound to the in vitro selected G-rich RNA. In this model system, the RNA adopts an intramolecular K(+)-stabilized G-quadruplex structure composed of three G-quartets and a mixed tetrad connected to an RNA duplex. The RGG peptide specifically binds to the duplex-quadruplex junction, the mixed tetrad, and the duplex region of the RNA through shape complementarity, cation-π interactions, and multiple hydrogen bonds. Many of these interactions critically depend on a type I β-turn, a secondary structure element whose formation was not previously recognized in the RGG motif of FMRP. RNA mutagenesis and footprinting experiments indicate that interactions of the peptide with the duplex-quadruplex junction and the duplex of RNA are equally important for affinity and specificity of the RGG-RNA complex formation. These results suggest that specific binding of cellular RNAs by FMRP may involve hydrogen bonding with RNA duplexes and that RNA duplex recognition can be a characteristic RNA binding feature for RGG motifs in other proteins.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem, UUUU, parallel, 4+0, 2(-P-P-P)
Cartoon-block schematics in six views (download the tarball)
List of 3 G-tetrads
1 glyco-bond=---- sugar=---- groove=---- planarity=0.484 type=other N+ nts=4 GGGG 1:A.G6,1:A.G9,1:A.G26,1:A.G18 2 glyco-bond=---- sugar=3333 groove=---- planarity=0.620 type=other O+ nts=4 GGGG 1:A.G11,1:A.G15,1:A.G20,1:A.G24 3 glyco-bond=---- sugar=---3 groove=---- planarity=0.317 type=saddle O+ nts=4 GGGG 1:A.G12,1:A.G16,1:A.G21,1:A.G25
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
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major N+ nts=4 GGGG 1:A.G6,1:A.G9,1:A.G26,1:A.G18 2 glyco-bond=---- sugar=--3- groove=---- Major-->WC O+ nts=4 GGGG 1:A.G16,1:A.G12,1:A.G25,1:A.G21 3 glyco-bond=---- sugar=3333 groove=---- Major-->WC O+ nts=4 GGGG 1:A.G15,1:A.G11,1:A.G24,1:A.G20 step#1 pp(><,inward) area=7.44 rise=3.50 twist=-35.5 step#2 mp(<<,backward) area=14.07 rise=3.75 twist=26.4 strand#1 RNA glyco-bond=--- sugar=--3 nts=3 GGG 1:A.G6,1:A.G16,1:A.G15 strand#2 RNA glyco-bond=--- sugar=--3 nts=3 GGG 1:A.G9,1:A.G12,1:A.G11 strand#3 RNA glyco-bond=--- sugar=-33 nts=3 GGG 1:A.G26,1:A.G25,1:A.G24 strand#4 RNA glyco-bond=--- sugar=--3 nts=3 GGG 1:A.G18,1:A.G21,1:A.G20 |
| 2 stacking diagrams | |
|
1 glyco-bond=---- sugar=---- groove=---- WC-->Major N+ nts=4 GGGG 1:A.G6,1:A.G9,1:A.G26,1:A.G18 |
|
2 glyco-bond=---- sugar=--3- groove=---- Major-->WC O+ nts=4 GGGG 1:A.G16,1:A.G12,1:A.G25,1:A.G21 |
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, 2 G-tetrads, 3 loops, INTRA-molecular, UUUU, parallel, 4+0, 2(-P-P-P)
|
1 glyco-bond=---- sugar=3333 groove=---- WC-->Major O+ nts=4 GGGG 1:A.G11,1:A.G15,1:A.G20,1:A.G24 2 glyco-bond=---- sugar=---3 groove=---- WC-->Major O+ nts=4 GGGG 1:A.G12,1:A.G16,1:A.G21,1:A.G25 step#1 pm(>>,forward) area=14.07 rise=3.75 twist=26.4 strand#1 U RNA glyco-bond=-- sugar=3- nts=2 GG 1:A.G11,1:A.G12 strand#2 U RNA glyco-bond=-- sugar=3- nts=2 GG 1:A.G15,1:A.G16 strand#3 U RNA glyco-bond=-- sugar=3- nts=2 GG 1:A.G20,1:A.G21 strand#4 U RNA glyco-bond=-- sugar=33 nts=2 GG 1:A.G24,1:A.G25 loop#1 type=propeller strands=[#1,#2] nts=2 AA 1:A.A13,1:A.A14 loop#2 type=propeller strands=[#2,#3] nts=3 AGU 1:A.A17,1:A.G18,1:A.U19 loop#3 type=propeller strands=[#3,#4] nts=2 CU 1:A.C22,1:A.U23 |
List of 1 non-stem G4-loop (including the two closing Gs)
1 type=lateral helix=#1 nts=4 GGUG 1:A.G6,1:A.G7,1:A.U8,1:A.G9