DSSR-curated G4 structure: PDB entry 5de8

Summary information

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: 6 G-tetrads, 2 G4 helices, 2 G4 stems, 2(-P-P-P), parallel(4+0), UUUU

Base-block schematics in six views

PyMOL session file	PDB file	View in 3Dmol.js

List of 6 G-tetrads

 1 glyco-bond=---- sugar=---- groove=---- planarity=0.484 type=other  nts=4 GGGG A.G6,A.G9,A.G26,A.G18
 2 glyco-bond=---- sugar=3333 groove=---- planarity=0.620 type=other  nts=4 GGGG A.G11,A.G15,A.G20,A.G24
 3 glyco-bond=---- sugar=---3 groove=---- planarity=0.317 type=saddle nts=4 GGGG A.G12,A.G16,A.G21,A.G25
 4 glyco-bond=---- sugar=---- groove=---- planarity=0.484 type=other  nts=4 GGGG C.G6,C.G9,C.G26,C.G18
 5 glyco-bond=---- sugar=33-3 groove=---- planarity=0.457 type=other  nts=4 GGGG C.G11,C.G15,C.G20,C.G24
 6 glyco-bond=---- sugar=---3 groove=---- planarity=0.279 type=other  nts=4 GGGG C.G12,C.G16,C.G21,C.G25

List of 2 G4-helices

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-tetrad layers, INTRA-molecular, with 1 stem

	1 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.G6,A.G9,A.G26,A.G18 2 glyco-bond=---- sugar=--3- groove=---- Major-->WC nts=4 GGGG A.G16,A.G12,A.G25,A.G21 3 glyco-bond=---- sugar=3333 groove=---- Major-->WC nts=4 GGGG A.G15,A.G11,A.G24,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 A.G6,A.G16,A.G15 strand#2 RNA glyco-bond=--- sugar=--3 nts=3 GGG A.G9,A.G12,A.G11 strand#3 RNA glyco-bond=--- sugar=-33 nts=3 GGG A.G26,A.G25,A.G24 strand#4 RNA glyco-bond=--- sugar=--3 nts=3 GGG A.G18,A.G21,A.G20 Download PDB file Interactive view in 3Dmol.js
2 stacking diagrams
	1 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG A.G6,A.G9,A.G26,A.G18 2 glyco-bond=---- sugar=--3- groove=---- Major-->WC nts=4 GGGG A.G16,A.G12,A.G25,A.G21 step#1 pp(><,inward) area=7.44 rise=3.50 twist=-35.5 Download PDB file Interactive view in 3Dmol.js
	2 glyco-bond=---- sugar=--3- groove=---- Major-->WC nts=4 GGGG A.G16,A.G12,A.G25,A.G21 3 glyco-bond=---- sugar=3333 groove=---- Major-->WC nts=4 GGGG A.G15,A.G11,A.G24,A.G20 step#2 mp(<<,backward) area=14.07 rise=3.75 twist=26.4 Download PDB file Interactive view in 3Dmol.js

Helix#2, 3 G-tetrad layers, INTRA-molecular, with 1 stem

	1 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG C.G6,C.G9,C.G26,C.G18 2 glyco-bond=---- sugar=--3- groove=---- Major-->WC nts=4 GGGG C.G16,C.G12,C.G25,C.G21 3 glyco-bond=---- sugar=333- groove=---- Major-->WC nts=4 GGGG C.G15,C.G11,C.G24,C.G20 step#1 pp(><,inward) area=8.14 rise=3.48 twist=-36.9 step#2 mp(<<,backward) area=15.93 rise=3.67 twist=24.2 strand#1 RNA glyco-bond=--- sugar=--3 nts=3 GGG C.G6,C.G16,C.G15 strand#2 RNA glyco-bond=--- sugar=--3 nts=3 GGG C.G9,C.G12,C.G11 strand#3 RNA glyco-bond=--- sugar=-33 nts=3 GGG C.G26,C.G25,C.G24 strand#4 RNA glyco-bond=--- sugar=--- nts=3 GGG C.G18,C.G21,C.G20 Download PDB file Interactive view in 3Dmol.js
2 stacking diagrams
	1 glyco-bond=---- sugar=---- groove=---- WC-->Major nts=4 GGGG C.G6,C.G9,C.G26,C.G18 2 glyco-bond=---- sugar=--3- groove=---- Major-->WC nts=4 GGGG C.G16,C.G12,C.G25,C.G21 step#1 pp(><,inward) area=8.14 rise=3.48 twist=-36.9 Download PDB file Interactive view in 3Dmol.js
	2 glyco-bond=---- sugar=--3- groove=---- Major-->WC nts=4 GGGG C.G16,C.G12,C.G25,C.G21 3 glyco-bond=---- sugar=333- groove=---- Major-->WC nts=4 GGGG C.G15,C.G11,C.G24,C.G20 step#2 mp(<<,backward) area=15.93 rise=3.67 twist=24.2 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, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)

 1  glyco-bond=---- sugar=3333 groove=---- WC-->Major nts=4 GGGG A.G11,A.G15,A.G20,A.G24
 2  glyco-bond=---- sugar=---3 groove=---- WC-->Major nts=4 GGGG A.G12,A.G16,A.G21,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 A.G11,A.G12
  strand#2  U RNA glyco-bond=-- sugar=3- nts=2 GG A.G15,A.G16
  strand#3  U RNA glyco-bond=-- sugar=3- nts=2 GG A.G20,A.G21
  strand#4  U RNA glyco-bond=-- sugar=33 nts=2 GG A.G24,A.G25
  loop#1 type=propeller strands=[#1,#2] nts=2 AA A.A13,A.A14
  loop#2 type=propeller strands=[#2,#3] nts=3 AGU A.A17,A.G18,A.U19
  loop#3 type=propeller strands=[#3,#4] nts=2 CU A.C22,A.U23

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Interactive view in 3Dmol.js

Stem#2, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)

 1  glyco-bond=---- sugar=33-3 groove=---- WC-->Major nts=4 GGGG C.G11,C.G15,C.G20,C.G24
 2  glyco-bond=---- sugar=---3 groove=---- WC-->Major nts=4 GGGG C.G12,C.G16,C.G21,C.G25
  step#1  pm(>>,forward)  area=15.93 rise=3.67 twist=24.2
  strand#1  U RNA glyco-bond=-- sugar=3- nts=2 GG C.G11,C.G12
  strand#2  U RNA glyco-bond=-- sugar=3- nts=2 GG C.G15,C.G16
  strand#3  U RNA glyco-bond=-- sugar=-- nts=2 GG C.G20,C.G21
  strand#4  U RNA glyco-bond=-- sugar=33 nts=2 GG C.G24,C.G25
  loop#1 type=propeller strands=[#1,#2] nts=2 AA C.A13,C.A14
  loop#2 type=propeller strands=[#2,#3] nts=3 AGU C.A17,C.G18,C.U19
  loop#3 type=propeller strands=[#3,#4] nts=2 CU C.C22,C.U23