期刊
NUCLEIC ACIDS RESEARCH
卷 38, 期 22, 页码 8370-8376出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq700
关键词
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资金
- Ministry of Science and Higher Education (Poland) [N-N301-0171634, PBZ-MNiSW-07/I/2007, PBZ-MNiI-2/1/2005, PBZ-KBN-124/P05/2004]
- European Community - Research Infrastructure Action through the 'Integrated Infrastructure Initiative' Integrating Activity on Synchrotron and Free Electron Laser Science [R II 3-CT-2004-506008]
- Foundation for Polish Science
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 A) and the other at 1.9 A. 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 center dot center dot center dot 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.
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