Summary information [schematics · tetrads · helices · stems · costacks · homepage]

PDB-id
5de5
Class
RNA binding protein-RNA
Method
X-ray (3.0 Å)
Summary
Crystal structure of the complex between human fmrp rgg motif and G-quadruplex RNA
Reference
Vasilyev, N., Polonskaia, A., Darnell, J.C., Darnell, R.B., Patel, D.J., 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.
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 · negative twist

Base-block schematics in six views [summary · tetrads · helices · stems · costacks · homepage]

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List of 6 G-tetrads [summary · schematics · helices · stems · costacks · homepage]

 1 glyco-bond=---- groove=---- planarity=0.489 type=other  nts=4 GGGG A.G6,A.G9,A.G26,A.G18
 2 glyco-bond=---- groove=---- planarity=0.555 type=other  nts=4 GGGG A.G11,A.G15,A.G20,A.G24
 3 glyco-bond=---- groove=---- planarity=0.272 type=saddle nts=4 GGGG A.G12,A.G16,A.G21,A.G25
 4 glyco-bond=---- groove=---- planarity=0.490 type=other  nts=4 GGGG C.G6,C.G9,C.G26,C.G18
 5 glyco-bond=---- groove=---- planarity=0.470 type=other  nts=4 GGGG C.G11,C.G15,C.G20,C.G24
 6 glyco-bond=---- groove=---- planarity=0.279 type=other  nts=4 GGGG C.G12,C.G16,C.G21,C.G25

List of 2 G4-helices [summary · schematics · tetrads · stems · costacks · homepage]

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=---- groove=---- WC-->Major nts=4 GGGG A.G6,A.G9,A.G26,A.G18
 2  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G16,A.G12,A.G25,A.G21
 3  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G15,A.G11,A.G24,A.G20
  step#1  pp(><,inward)   area=7.84  rise=3.48 twist=-37.6
  step#2  mp(<<,backward) area=13.71 rise=3.69 twist=27.1
  strand#1 RNA glyco-bond=--- nts=3 GGG A.G6,A.G16,A.G15
  strand#2 RNA glyco-bond=--- nts=3 GGG A.G9,A.G12,A.G11
  strand#3 RNA glyco-bond=--- nts=3 GGG A.G26,A.G25,A.G24
  strand#4 RNA glyco-bond=--- nts=3 GGG A.G18,A.G21,A.G20

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2 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G6,A.G9,A.G26,A.G18
2 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G16,A.G12,A.G25,A.G21
step#1 pp(><,inward) area=7.84 rise=3.48 twist=-37.6

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 2  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G16,A.G12,A.G25,A.G21
3 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG A.G15,A.G11,A.G24,A.G20
step#2 mp(<<,backward) area=13.71 rise=3.69 twist=27.1

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

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG C.G6,C.G9,C.G26,C.G18
 2  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.G16,C.G12,C.G25,C.G21
 3  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.G15,C.G11,C.G24,C.G20
  step#1  pp(><,inward)   area=9.09  rise=3.46 twist=-38.2
  step#2  mp(<<,backward) area=14.12 rise=3.66 twist=25.6
  strand#1 RNA glyco-bond=--- nts=3 GGG C.G6,C.G16,C.G15
  strand#2 RNA glyco-bond=--- nts=3 GGG C.G9,C.G12,C.G11
  strand#3 RNA glyco-bond=--- nts=3 GGG C.G26,C.G25,C.G24
  strand#4 RNA glyco-bond=--- nts=3 GGG C.G18,C.G21,C.G20

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2 stacking diagrams
 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG C.G6,C.G9,C.G26,C.G18
2 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.G16,C.G12,C.G25,C.G21
step#1 pp(><,inward) area=9.09 rise=3.46 twist=-38.2

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 2  glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.G16,C.G12,C.G25,C.G21
3 glyco-bond=---- groove=---- Major-->WC nts=4 GGGG C.G15,C.G11,C.G24,C.G20
step#2 mp(<<,backward) area=14.12 rise=3.66 twist=25.6

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List of 2 G4-stems [summary · schematics · tetrads · helices · costacks · homepage]

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=---- groove=---- WC-->Major nts=4 GGGG A.G11,A.G15,A.G20,A.G24
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG A.G12,A.G16,A.G21,A.G25
  step#1  pm(>>,forward)  area=13.71 rise=3.69 twist=27.1
  strand#1  U RNA glyco-bond=-- nts=2 GG A.G11,A.G12
  strand#2  U RNA glyco-bond=-- nts=2 GG A.G15,A.G16
  strand#3  U RNA glyco-bond=-- nts=2 GG A.G20,A.G21
  strand#4  U RNA glyco-bond=-- 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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Stem#2, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUU, parallel, 2(-P-P-P), parallel(4+0)

 1  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG C.G11,C.G15,C.G20,C.G24
 2  glyco-bond=---- groove=---- WC-->Major nts=4 GGGG C.G12,C.G16,C.G21,C.G25
  step#1  pm(>>,forward)  area=14.12 rise=3.66 twist=25.6
  strand#1  U RNA glyco-bond=-- nts=2 GG C.G11,C.G12
  strand#2  U RNA glyco-bond=-- nts=2 GG C.G15,C.G16
  strand#3  U RNA glyco-bond=-- nts=2 GG C.G20,C.G21
  strand#4  U RNA glyco-bond=-- 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

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List of 0 G4 coaxial stacks [summary · schematics · tetrads · helices · stems · homepage]

List of 2 non-stem G4-loops (including the two closing Gs)

 1 type=lateral   helix=#1 nts=4 GGUG A.G6,A.G7,A.U8,A.G9
 2 type=lateral   helix=#2 nts=4 GGUG C.G6,C.G7,C.U8,C.G9