1ZEV

Crystal Structure of a Pathogenic RNA: CUG Repeats

Summary for 1ZEV

• Entry DOI: 10.2210/pdb1zev/pdb
• Descriptor: 5'-R(*CP*UP*GP*CP*UP*GP*CP*UP*GP*CP*UP*GP*CP*UP*GP*CP*UP*G)-3' (2 entities in total)
• Functional Keywords: uu mismatches, triplet repeats, causitive agent of myotonic dystrophy type i, rna
• Total number of polymer chains: 2
• Total formula weight: 11388.73

Authors

Mooers, B.H.,Logue, J.S.,Berglund, J.A. (deposition date: 2005-04-19, release date: 2005-10-25, Last modification date: 2024-02-14)

Primary citation

Mooers, B.H.,Logue, J.S.,Berglund, J.A.
The structural basis of myotonic dystrophy from the crystal structure of CUG repeats.
Proc.Natl.Acad.Sci.Usa, 102:16626-16631, 2005

PubMed Abstract: Myotonic dystrophy (DM) type 1 is associated with an expansion of (>50) CTG repeats within the 3' untranslated region (UTR) of the dystrophin myotonin protein kinase gene (dmpk). In the corresponding mRNA transcript, the CUG repeats form an extended stem-loop structure. The double-stranded RNA of the stem sequesters RNA binding proteins away from their normal cellular targets resulting in aberrant transcription, alternative splicing patterns, or both, thereby leading to DM. To better understand the structural basis of DM type 1, we determined to 1.58-A resolution the x-ray crystal structure of an 18-bp RNA containing six CUG repeats. The CUG repeats form antiparallel double-stranded helices that stack end-on-end in the crystal to form infinite, pseudocontinuous helices similar to the long CUG stem loops formed by the expanded CUG repeats in DM type 1. The CUG helix is very similar in structure to A-form RNA with the exception of the unique U-U mismatches. This structure provides a high-resolution view of a toxic, trinucleotide repeat RNA.

PubMed: 16269545
DOI: 10.1073/pnas.0505873102

Experimental method

X-RAY DIFFRACTION (1.58 Å)