Structural and mechanistic insights into an archaeal DNA-guided Argonaute protein
| Autor: | Adrian Zander, Sabine Schneider, Ronan M. Keegan, Sarah Willkomm, Dina Grohmann, Tobias Restle, Christine A. Oellig |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Genetics biology Immunology Methanocaldococcus jannaschii Cell Biology Plasma protein binding Computational biology Argonaute biology.organism_classification Applied Microbiology and Biotechnology Microbiology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Protein structure chemistry RNA interference Protein folding Gene 030217 neurology & neurosurgery DNA |
| Zdroj: | Nature Microbiology. 2 |
| ISSN: | 2058-5276 |
| DOI: | 10.1038/nmicrobiol.2017.35 |
| Popis: | Argonaute (Ago) proteins in eukaryotes are known as key players in post-transcriptional gene silencing1, while recent studies on prokaryotic Agos hint at their role in the protection against invading DNA2,3. Here, we present crystal structures of the apo enzyme and a binary Ago-guide complex of the archaeal Methanocaldococcus jannaschii (Mj) Ago. Binding of a guide DNA leads to large structural rearrangements. This includes the structural transformation of a hinge region containing a switch helix, which has been shown for human Ago2 to be critical for the dynamic target search process4-6. To identify key residues crucial for MjAgo function, we analysed the effect of several MjAgo mutants. We observe that the nature of the 3' and 5' nucleotides in particular, as well as the switch helix, appear to impact MjAgo cleavage activity. In summary, we provide insights into the molecular mechanisms that drive DNA-guided DNA silencing by an archaeal Ago. |
| Databáze: | OpenAIRE |
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