Slicer and the Argonautes

Faehnle, C. R., Elkayam, E., Haase, A. D., Hannon, G. J., Joshua-Tor, L. (January 2014) Slicer and the Argonautes. Biophysical Journal, 106 (2; Sup). 455A-455A. ISSN 0006-3495

DOI: 10.1016/j.bpj.2013.11.2576


Argonautes are the central protein component in small RNA silencing pathways. Of the four human Argonautes (hAgo1-4) only hAgo2 is an active slicer. We have determined structures of the catalytically active hAgo2 as well as the catalytically inactive hAgo1, both bound to discrete miRNAs. The structures are strikingly similar. 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.

Item Type: Paper
Additional Information: Meeting Abstract
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > argonaute proteins
Publication Type > Meeting Abstract
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Joshua-Tor lab
Depositing User: Matt Covey
Date: 28 January 2014
Date Deposited: 11 Jul 2014 16:42
Last Modified: 06 Feb 2018 16:16

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