4KRF

Structure of Human Argonaute-1 let-7 complex

Summary for 4KRF

• Entry DOI: 10.2210/pdb4krf/pdb
• Related: 4KRE
• Descriptor: Protein argonaute-1, RNA (5'-R(P*UP*GP*AP*GP*GP*UP*AP*GP*UP*AP*GP*GP*UP*UP*GP*UP*AP*UP*AP*GP*UP*U)-3') (3 entities in total)
• Functional Keywords: eukaryotic argonaute, gene regulation, rnai, slicer, transcription-rna complex, transcription/rna
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, P-body: Q9UL18
• Total number of polymer chains: 2
• Total formula weight: 104538.58

Authors

Faehnle, C.R.,Elkayam, E.,Joshua-Tor, L. (deposition date: 2013-05-16, release date: 2013-06-19, Last modification date: 2024-02-28)

Primary citation

Faehnle, C.R.,Elkayam, E.,Haase, A.D.,Hannon, G.J.,Joshua-Tor, L.
The making of a slicer: activation of human argonaute-1.
Cell Rep, 3:1901-1909, 2013

PubMed 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.

PubMed: 23746446
DOI: 10.1016/j.celrep.2013.05.033

Experimental method

X-RAY DIFFRACTION (2.101 Å)