Structural highlights
Publication Abstract from PubMed
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 A resolution and hAgo1 loaded with let-7 microRNA to 2.1 A. 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.
The making of a slicer: activation of human argonaute-1.,Faehnle CR, Elkayam E, Haase AD, Hannon GJ, Joshua-Tor L Cell Rep. 2013 Jun 27;3(6):1901-9. doi: 10.1016/j.celrep.2013.05.033. Epub 2013, Jun 6. PMID:23746446[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Faehnle CR, Elkayam E, Haase AD, Hannon GJ, Joshua-Tor L. The making of a slicer: activation of human argonaute-1. Cell Rep. 2013 Jun 27;3(6):1901-9. doi: 10.1016/j.celrep.2013.05.033. Epub 2013, Jun 6. PMID:23746446 doi:10.1016/j.celrep.2013.05.033
