Journal
NUCLEIC ACIDS RESEARCH
Volume 44, Issue 12, Pages 5944-5956Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkw388
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Funding
- French 'Ministere de la recherche et de l'enseignement'
- Polish Ministry of Higher Education and Science (Mobility Plus programme) [1103/MOB/2013/0]
- CNRS
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Since the work of Alexander Rich, who solved the first Z-DNA crystal structure, we have known that d(CpG) steps can adopt a particular structure that leads to forming left-handed helices. However, it is still largely unrecognized that other sequences can adopt 'left-handed' conformations in DNA and RNA, in double as well as single stranded contexts. These 'Z-like' steps involve the coexistence of several rare structural features: C2'-endo puckering, a syn nucleotide and a lone pair-pi stacking between a ribose O4' atom and a nucleobase. This particular arrangement induces a conformational stress in the RNA backbone, which limits the occurrence of Z-like steps to approximate to 0.1% of all dinucleotide steps in the PDB. Here, we report over 600 instances of Z-like steps, which are located within r(UNCG) tetraloops but also in small and large RNAs including riboswitches, ribozymes and ribosomes. Given their complexity, Z-like steps are probably associated with slow folding kinetics and once formed could lock a fold through the formation of unique long-range contacts. Proteins involved in immunologic response also specifically recognize/induce these peculiar folds. Thus, characterizing the conformational features of these motifs could be a key to understanding the immune response at a structural level.
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