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The genomic HDV ribozyme utilizes a previously unnoticed U-turn motif to accomplish fast site-specific catalysis.


ABSTRACT: The genome of the human hepatitis delta virus (HDV) harbors a self-cleaving catalytic RNA motif, the genomic HDV ribozyme, whose crystal structure shows the dangling nucleotides 5' of the cleavage site projecting away from the catalytic core. This 5'-sequence contains a clinically conserved U-1 that we find to be essential for fast cleavage, as the order of activity follows U-1 > C-1 > A-1 > G-1, with a >25-fold activity loss from U-1 to G-1. Terbium(III) footprinting detects conformations for the P1.1 stem, the cleavage site wobble pair and the A-minor motif of the catalytic trefoil turn that depend on the identity of the N-1 base. The most tightly folded catalytic core, resembling that of the reaction product, is found in the U-1 wild-type precursor. Molecular dynamics simulations demonstrate that a U-1 forms the most robust kink around the scissile phosphate, exposing it to the catalytic C75 in a previously unnoticed U-turn motif found also, for example, in the hammerhead ribozyme and tRNAs. Strikingly, we find that the common structural U-turn motif serves distinct functions in the HDV and hammerhead ribozymes.

SUBMITTER: Sefcikova J 

PROVIDER: S-EPMC1874588 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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The genomic HDV ribozyme utilizes a previously unnoticed U-turn motif to accomplish fast site-specific catalysis.

Sefcikova Jana J   Krasovska Maryna V MV   Sponer Jirí J   Walter Nils G NG  

Nucleic acids research 20070302 6


The genome of the human hepatitis delta virus (HDV) harbors a self-cleaving catalytic RNA motif, the genomic HDV ribozyme, whose crystal structure shows the dangling nucleotides 5' of the cleavage site projecting away from the catalytic core. This 5'-sequence contains a clinically conserved U-1 that we find to be essential for fast cleavage, as the order of activity follows U-1 > C-1 > A-1 > G-1, with a >25-fold activity loss from U-1 to G-1. Terbium(III) footprinting detects conformations for t  ...[more]

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