Summary information and primary citation
- PDB-id
- 4kre; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- transcription-RNA
- Method
- X-ray (1.754 Å)
- Summary
- Structure of human argonaute-1 bound to endogenous sf9 RNA
- Reference
- Faehnle CR, Elkayam E, Haase AD, Hannon GJ, Joshua-Tor L (2013): "The making of a slicer: activation of human argonaute-1." Cell Rep, 3, 1901-1909. doi: 10.1016/j.celrep.2013.05.033.
- Abstract
- Argonautes are the central protein component in small RNA silencing pathways. Of the four human Argonautes (hAgo1-hAgo4) only hAgo2 is an active slicer. We determined the structure of hAgo1 bound to endogenous copurified RNAs to 1.75 Å resolution and hAgo1 loaded with let-7 microRNA to 2.1 Å. Both structures are strikingly similar to the structures of hAgo2. A conserved catalytic tetrad within the PIWI domain of hAgo2 is required for its slicing activity. Completion of the tetrad, combined with a mutation on a loop adjacent to the active site of hAgo1, results in slicer activity that is substantially enhanced by swapping in the N domain of hAgo2. hAgo3, with an intact tetrad, becomes an active slicer by swapping the N domain of hAgo2 without additional mutations. Intriguingly, the elements that make Argonaute an active slicer involve a sophisticated interplay between the active site and more distant regions of the enzyme.
