3NJ7

1.9 A resolution X-ray structure of (GGCAGCAGCC)2

Summary for 3NJ7

• Entry DOI: 10.2210/pdb3nj7/pdb
• Related: 3NJ6
• Descriptor: 5'-R(*GP*GP*CP*AP*GP*CP*AP*GP*CP*C)-3', SULFATE ION (3 entities in total)
• Functional Keywords: cag repeats, poly-q diseases, rna
• Total number of polymer chains: 6
• Total formula weight: 19866.40

Authors

Kiliszek, A.,Kierzek, R.,Krzyzosiak, W.J.,Rypniewski, W. (deposition date: 2010-06-17, release date: 2010-08-25, Last modification date: 2023-09-06)

Primary citation

Kiliszek, A.,Kierzek, R.,Krzyzosiak, W.J.,Rypniewski, W.
Atomic resolution structure of CAG RNA repeats: structural insights and implications for the trinucleotide repeat expansion diseases.
Nucleic Acids Res., 38:8370-8376, 2010

PubMed Abstract: CAG repeats occur predominantly in the coding regions of human genes, which suggests their functional importance. In some genes, these sequences can undergo pathogenic expansions leading to neurodegenerative polyglutamine (poly-Q) diseases. The mutant transcripts containing expanded CAG repeats possibly contribute to pathogenesis in addition to the well-known pathogenic effects of mutant proteins. We have analysed two crystal forms of RNA duplexes containing CAG repeats: (GGCAGCAGCC)(2). One of the structures has been determined at atomic resolution (0.95 Å) and the other at 1.9 Å. The duplexes include non-canonical A-A pairs that fit remarkably well within a regular A-helix. All the adenosines are in the anti-conformation and the only interaction within each A-A pair is a single C2-H2···N1 hydrogen bond. Both adenosines in each A-A pair are shifted towards the major groove, although to different extents; the A which is the H-bond donor stands out more (the 'thumbs-up' conformation). The main effect on the helix conformation is a local unwinding. The CAG repeats and the previously examined CUG structures share a similar pattern of electrostatic charge distribution in the minor groove, which could explain their affinity for the pathogenesis-related MBNL1 protein.

PubMed: 20702420
DOI: 10.1093/nar/gkq700

Experimental method

X-RAY DIFFRACTION (1.904 Å)