1noq
From Proteopedia
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e-motif structure
Overview
Recent molecular genetics studies have revealed a correlation between, spontaneous, progressive expansion of several DNA trinucleotide repeats, and certain hereditary neurodegenerative diseases. Triplet repeat (TR), sequences may be present in structured forms that can mediate the, processes interrupting normal cellular replication, transcription, or, repair activities, eventually leading to gene mutation. Using high, resolution NMR spectroscopy and other biophysical methods, we probed the, solution structures and properties of single-stranded TR sequences. These, studies have led to the discovery of a new duplex motif (e-motif), present, in CCG repeats, and to the elucidation of the structure of the (CTG)3, duplex. In this paper we provide a global picture of the solution behavior, of the human disease-related CXG (X = A, C, G, or T) and the comparison, GXC (X = A, or T) TR sequences. All six triplet repeats form antiparallel, duplexes. The mismatched bases in CAG and CGG repeat duplexes are rather, flexible and they do not appear to form stable, paired conformations. By, comparison, GAC repeat duplexes and their mismatched A residues are, well-structured. Most interestingly, the structures of the disease-related, CXG repeats exhibit a propensity for folding at chain lengths as short as, 12 residues. Furthermore, the energy barrier for the formation of, homo-duplexes from the corresponding complementary hetero-duplexes are, much lower for the CXG TR sequences than for the GAC or GTC TR sequences., These results provide insights into the conformation and physiochemical, properties of TR sequences. Thus, a basis is provided for further studies, of the behavior of long TR sequences in an effort to elucidate the, molecular mechanisms of in vivo expansion and function of TR sequences.
About this Structure
1NOQ is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Genetically unstable CXG repeats are structurally dynamic and have a high propensity for folding. An NMR and UV spectroscopic study., Zheng M, Huang X, Smith GK, Yang X, Gao X, J Mol Biol. 1996 Nov 29;264(2):323-36. PMID:8951379
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