Summary information

PDB id
6e8s
Class
RNA
Method
X-ray (2.35 Å)
Summary
Structure of the imango-iii aptamer bound to to1-biotin
Reference
Trachman 3rd RJ, Autour A, Jeng SCY, Abdolahzadeh A, Andreoni A, Cojocaru R, Garipov R, Dolgosheina EV, Knutson JR, Ryckelynck M, Unrau PJ, Ferre-D'Amare AR (2019): "Structure and functional reselection of the Mango-III fluorogenic RNA aptamer." Nat. Chem. Biol., 15, 472-479. doi: 10.1038/s41589-019-0267-9.
Abstract
Several turn-on RNA aptamers that activate small-molecule fluorophores have been selected in vitro. Among these, the ~30 nucleotide Mango-III is notable because it binds the thiazole orange derivative TO1-Biotin with high affinity and fluoresces brightly (quantum yield 0.55). Uniquely among related aptamers, Mango-III exhibits biphasic thermal melting, characteristic of molecules with tertiary structure. We report crystal structures of TO1-Biotin complexes of Mango-III, a structure-guided mutant Mango-III(A10U), and a functionally reselected mutant iMango-III. The structures reveal a globular architecture arising from an unprecedented pseudoknot-like connectivity between a G-quadruplex and an embedded non-canonical duplex. The fluorophore is restrained into a planar conformation by the G-quadruplex, a lone, long-range trans Watson-Crick pair (whose A10U mutation increases quantum yield to 0.66), and a pyrimidine perpendicular to the nucleobase planes of those motifs. The improved iMango-III and Mango-III(A10U) fluoresce ~50% brighter than enhanced green fluorescent protein, making them suitable tags for live cell RNA visualization.
G4 notes
4 G-tetrads, 2 G4 helices, 2 G4 stems, 2(-P-P-Lw), hybrid-2R(3+1), UUUD

Base-block schematics in six views

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List of 4 G-tetrads

 1 glyco-bond=---s sugar=-33- groove=--wn planarity=0.480 type=other  nts=4 GGGG A.G9,A.G13,A.G18,A.G25
 2 glyco-bond=---s sugar=-3-3 groove=--wn planarity=0.294 type=other  nts=4 GGGG A.G10,A.G14,A.G19,A.G23
 3 glyco-bond=---s sugar=-33- groove=--wn planarity=0.462 type=other  nts=4 GGGG B.G9,B.G13,B.G18,B.G25
 4 glyco-bond=---s sugar=-3-3 groove=--wn planarity=0.286 type=other  nts=4 GGGG B.G10,B.G14,B.G19,B.G23

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, 2 G-tetrad layers, INTRA-molecular, with 1 stem

 1  glyco-bond=---s sugar=-33- groove=--wn WC-->Major nts=4 GGGG A.G9,A.G13,A.G18,A.G25
 2  glyco-bond=---s sugar=-3-3 groove=--wn WC-->Major nts=4 GGGG A.G10,A.G14,A.G19,A.G23
  step#1  pm(>>,forward)  area=10.52 rise=3.48 twist=28.7
  strand#1 RNA glyco-bond=-- sugar=-- nts=2 GG A.G9,A.G10
  strand#2 RNA glyco-bond=-- sugar=33 nts=2 GG A.G13,A.G14
  strand#3 RNA glyco-bond=-- sugar=3- nts=2 GG A.G18,A.G19
  strand#4 RNA glyco-bond=ss sugar=-3 nts=2 GG A.G25,A.G23

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1 stacking diagram 
 1  glyco-bond=---s sugar=-33- groove=--wn WC-->Major nts=4 GGGG A.G9,A.G13,A.G18,A.G25
 2  glyco-bond=---s sugar=-3-3 groove=--wn WC-->Major nts=4 GGGG A.G10,A.G14,A.G19,A.G23
  step#1  pm(>>,forward)  area=10.52 rise=3.48 twist=28.7

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

 1  glyco-bond=---s sugar=-33- groove=--wn WC-->Major nts=4 GGGG B.G9,B.G13,B.G18,B.G25
 2  glyco-bond=---s sugar=-3-3 groove=--wn WC-->Major nts=4 GGGG B.G10,B.G14,B.G19,B.G23
  step#1  pm(>>,forward)  area=11.29 rise=3.45 twist=28.7
  strand#1 RNA glyco-bond=-- sugar=-- nts=2 GG B.G9,B.G10
  strand#2 RNA glyco-bond=-- sugar=33 nts=2 GG B.G13,B.G14
  strand#3 RNA glyco-bond=-- sugar=3- nts=2 GG B.G18,B.G19
  strand#4 RNA glyco-bond=ss sugar=-3 nts=2 GG B.G25,B.G23

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1 stacking diagram 
 1  glyco-bond=---s sugar=-33- groove=--wn WC-->Major nts=4 GGGG B.G9,B.G13,B.G18,B.G25
 2  glyco-bond=---s sugar=-3-3 groove=--wn WC-->Major nts=4 GGGG B.G10,B.G14,B.G19,B.G23
  step#1  pm(>>,forward)  area=11.29 rise=3.45 twist=28.7

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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, UUUD, hybrid-(mixed), 2(-P-P-Lw), hybrid-2R(3+1)

 1  glyco-bond=---s sugar=-33- groove=--wn WC-->Major nts=4 GGGG A.G9,A.G13,A.G18,A.G25
 2  glyco-bond=---s sugar=-3-3 groove=--wn WC-->Major nts=4 GGGG A.G10,A.G14,A.G19,A.G23
  step#1  pm(>>,forward)  area=10.52 rise=3.48 twist=28.7
  strand#1  U RNA glyco-bond=-- sugar=-- nts=2 GG A.G9,A.G10
  strand#2  U RNA glyco-bond=-- sugar=33 nts=2 GG A.G13,A.G14
  strand#3  U RNA glyco-bond=-- sugar=3- nts=2 GG A.G18,A.G19
  strand#4* D RNA glyco-bond=ss sugar=-3 nts=2 GG A.G25,A.G23 bulged-nts=1 U A.U24
  loop#1 type=propeller strands=[#1,#2] nts=2 AA A.A11,A.A12
  loop#2 type=propeller strands=[#2,#3] nts=3 AUU A.A15,A.U16,A.U17
  loop#3 type=lateral   strands=[#3,#4] nts=3 UAU A.U20,A.A21,A.U22

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Stem#2, 2 G-tetrad layers, 3 loops, INTRA-molecular, UUUD, hybrid-(mixed), 2(-P-P-Lw), hybrid-2R(3+1)

 1  glyco-bond=---s sugar=-33- groove=--wn WC-->Major nts=4 GGGG B.G9,B.G13,B.G18,B.G25
 2  glyco-bond=---s sugar=-3-3 groove=--wn WC-->Major nts=4 GGGG B.G10,B.G14,B.G19,B.G23
  step#1  pm(>>,forward)  area=11.29 rise=3.45 twist=28.7
  strand#1  U RNA glyco-bond=-- sugar=-- nts=2 GG B.G9,B.G10
  strand#2  U RNA glyco-bond=-- sugar=33 nts=2 GG B.G13,B.G14
  strand#3  U RNA glyco-bond=-- sugar=3- nts=2 GG B.G18,B.G19
  strand#4* D RNA glyco-bond=ss sugar=-3 nts=2 GG B.G25,B.G23 bulged-nts=1 U B.U24
  loop#1 type=propeller strands=[#1,#2] nts=2 AA B.A11,B.A12
  loop#2 type=propeller strands=[#2,#3] nts=3 AUU B.A15,B.U16,B.U17
  loop#3 type=lateral   strands=[#3,#4] nts=3 UAU B.U20,B.A21,B.U22

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