Willkomm, Sarah and Oellig, Christine A. and Zander, Adrian and Restle, Tobias and Keegan, Ronan and Grohmann, Dina and Schneider, Sabine (2017) Structural and mechanistic insights into an archaeal DNA-guided Argonaute protein. NATURE MICROBIOLOGY, 2 (6): 17035. ISSN 2058-5276,
Full text not available from this repository. (Request a copy)Abstract
Argonaute (Ago) proteins in eukaryotes are known as key players in post-transcriptional gene silencing(1), while recent studies on prokaryotic Agos hint at their role in the protection against invading DNA(2,3). 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 process(4-6). 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CRYSTAL-STRUCTURE; THERMUS-THERMOPHILUS; BACTERIAL ARGONAUTE; SLICER ACTIVITY; RNA; DOMAIN; REFINEMENT; RECOGNITION; CLEAVAGE; MODEL; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Mikrobiologie > Prof. Dr. Dina Grohmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:10 |
| Last Modified: | 25 Feb 2019 12:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/738 |
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