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New tools provide a second look at HDV ribozyme structure, dynamics and cleavage
- Source :
- Nucleic Acids Research, Nucleic acids research, vol 42, iss 20, Kapral, Gary J; Jain, Swati; Noeske, Jonas; Doudna, Jennifer A; Richardson, David C; & Richardson, Jane S. (2014). New tools provide a second look at HDV ribozyme structure, dynamics and cleavage.. Nucleic acids research, 42(20), 12833-12846. doi: 10.1093/nar/gku992. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/1tn4870w
- Publication Year :
- 2014
- Publisher :
- Oxford University Press, 2014.
-
Abstract
- The hepatitis delta virus (HDV) ribozyme is a self-cleaving RNA enzyme essential for processing viral transcripts during rolling circle viral replication. The first crystal structure of the cleaved ribozyme was solved in 1998, followed by structures of uncleaved, mutant-inhibited and ion-complexed forms. Recently, methods have been developed that make the task of modeling RNA structure and dynamics significantly easier and more reliable. We have used ERRASER and PHENIX to rebuild and re-refine the cleaved and cis-acting C75U-inhibited structures of the HDV ribozyme. The results correct local conformations and identify alternates for RNA residues, many in functionally important regions, leading to improved R values and model validation statistics for both structures. We compare the rebuilt structures to a higher resolution, trans-acting deoxy-inhibited structure of the ribozyme, and conclude that although both inhibited structures are consistent with the currently accepted hammerhead-like mechanism of cleavage, they do not add direct structural evidence to the biochemical and modeling data. However, the rebuilt structures (PDBs: 4PR6, 4PRF) provide a more robust starting point for research on the dynamics and catalytic mechanism of the HDV ribozyme and demonstrate the power of new techniques to make significant improvements in RNA structures that impact biologically relevant conclusions.
- Subjects :
- Models, Molecular
U1 Small Nuclear
Computational biology
Biology
Ribonucleoprotein, U1 Small Nuclear
Models
Information and Computing Sciences
Genetics
RNA, Catalytic
Base Pairing
Ligase ribozyme
Catalytic
RNA Cleavage
Ribozyme
Molecular
Ribonucleoprotein
Biological Sciences
Stem-loop
Virology
GlmS glucosamine-6-phosphate activated ribozyme
biology.protein
RNA
Nucleic Acid Conformation
Mammalian CPEB3 ribozyme
Hepatitis Delta Virus
Hairpin ribozyme
VS ribozyme
Environmental Sciences
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 13624962 and 03051048
- Volume :
- 42
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....d55d67051bcd218b1ed2e5d8cf3abc9b