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Nucleic Acids Res ; 44(12): 5944-56, 2016 07 08.
Article in English | MEDLINE | ID: mdl-27151194

ABSTRACT

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: a C2'-endo puckering, a syn nucleotide and a lone pair-π 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 ≈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.


Subject(s)
DNA, Z-Form/chemistry , RNA, Catalytic/chemistry , RNA/chemistry , Ribosomes/chemistry , Riboswitch/genetics , Base Pairing , DNA, Z-Form/genetics , DNA, Z-Form/immunology , Escherichia coli/chemistry , Escherichia coli/genetics , Escherichia coli/immunology , Humans , Immunity, Innate , Kinetics , Models, Molecular , Nucleic Acid Conformation , RNA/genetics , RNA/immunology , RNA Folding , RNA, Catalytic/genetics , RNA, Catalytic/immunology , Ribosomes/genetics , Ribosomes/immunology , Riboswitch/immunology , Saccharomyces cerevisiae/chemistry , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/immunology
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