4FNJ

Utilizing the GAAA tetraloop/receptor to facilitate crystal packing and structure determination of a CUG RNA helix

Summary for 4FNJ

• Entry DOI: 10.2210/pdb4fnj/pdb
• Descriptor: RNA (35-MER), MAGNESIUM ION (3 entities in total)
• Functional Keywords: cug repeat gaaa tetraloop/receptor, toxic rna, rna
• Biological source: synthetic construct (artificial)
• Total number of polymer chains: 1
• Total formula weight: 11375.22

Authors

Coonrod, L.A.,Lohman, J.R.,Berglund, J.A. (deposition date: 2012-06-19, release date: 2012-10-17, Last modification date: 2024-02-28)

Primary citation

Coonrod, L.A.,Lohman, J.R.,Berglund, J.A.
Utilizing the GAAA Tetraloop/Receptor To Facilitate Crystal Packing and Determination of the Structure of a CUG RNA Helix.
Biochemistry, 51:8330-8337, 2012

PubMed Abstract: Myotonic dystrophy type 1 (DM1) is a microsatellite expansion disorder caused by the aberrant expansion of CTG repeats in the 3'-untranslated region of the DMPK gene. When transcribed, the toxic RNA CUG repeats sequester RNA binding proteins, which leads to disease symptoms. The expanded CUG repeats can adopt a double-stranded structure, and targeting this helix is a therapeutic strategy for DM1. To improve our understanding of the 5'CUG/3'GUC motif and how it may interact with proteins and small molecules, we designed a short CUG helix attached to a GAAA tetraloop/receptor to facilitate crystal packing. Here we report the highest-resolution structure (1.95 Å) to date of a GAAA tetraloop/receptor and the CUG helix it was used to crystallize. Within the CUG helix, we identify two different forms of noncanonical U-U pairs and reconfirm that CUG repeats are essentially A-form. An analysis of all noncanonical U-U pairs in the context of CUG repeats revealed six different classes of conformations that the noncanonical U-U pairs are able to adopt.

PubMed: 23025897
DOI: 10.1021/bi300829w

Experimental method

X-RAY DIFFRACTION (1.95 Å)