3SYW

Crystal Structure of the Triplet Repeat in Myotonic Dystrophy Reveals Heterogeneous 1x1 Nucleotide UU Internal Loop Conformations


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.168 

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This is version 1.2 of the entry. See complete history


Literature

Crystal Structure of the Triplet Repeat in Myotonic Dystrophy Reveals Heterogeneous 1x1 Nucleotide UU Internal Loop Conformations

Kumar, A.Park, H.Fang, P.Parkesh, R.Guo, M.Nettles, K.W.Disney, M.D.

(2011) Biochemistry 50: 9928-9935

  • DOI: https://doi.org/10.1021/bi2013068
  • Primary Citation of Related Structures:  
    3SYW, 3SZX

  • PubMed Abstract: 

    RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures of a model DM1 triplet repeating construct, 5'r[UUGGGC(CUG)(3)GUCC](2), refined to 2.20 and 1.52 Å resolution are disclosed. Here, differences in the orientation of the 5' dangling UU end between the two structures induce changes in the backbone groove width, which reveals that noncanonical 1 × 1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 Å structure, CUGa, the 5' UU forms a one hydrogen-bonded pair with a 5' UU of a neighboring helix in the unit cell to form a pseudoinfinite helix. The central 1 × 1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1 × 1 nucleotide UU internal loops each form a one-hydrogen bond pair. In the 1.52 Å structure, CUGb, the 5' UU dangling end is tucked into the major groove of the duplex. While the canonically paired bases show no change in base pairing, in CUGb the terminal 1 × 1 nucleotide UU internal loops now form two hydrogen-bonded pairs. Thus, the shift in the major groove induced by the 5' UU dangling end alters noncanonical base patterns. Collectively, these structures indicate that 1 × 1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands.


  • Organizational Affiliation

    Department of Chemistry, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, United States.


Macromolecules

Find similar nucleic acids by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains LengthOrganismImage
RNA (5'-R(*UP*UP*GP*GP*GP*CP*CP*UP*GP*CP*UP*GP*CP*UP*GP*GP*UP*CP*C)-3')
A, B
19N/A
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.187 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.168 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.535α = 90
b = 46.535β = 90
c = 135.001γ = 120
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-25
    Type: Initial release
  • Version 1.1: 2024-02-28
    Changes: Data collection, Database references, Derived calculations
  • Version 1.2: 2024-03-13
    Changes: Source and taxonomy, Structure summary