6N4O

Human Argonaute2-miR-122 bound to a seed and supplementary paired target

Summary for 6N4O

• Entry DOI: 10.2210/pdb6n4o/pdb
• Descriptor: Protein argonaute-2, RNA (5'-R(P*UP*GP*GP*AP*GP*UP*GP*UP*GP*AP*CP*AP*AP*UP*GP*GP*UP*GP*UP*UP*U)-3'), RNA (5'-R(*CP*CP*AP*UP*UP*GP*UP*CP*AP*CP*AP*CP*UP*CP*CP*AP*AP*A)-3') (3 entities in total)
• Functional Keywords: rna-binding protein, microrna, target directed microrna decay, hydrolase-rna complex, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 109782.63

Authors

Sheu-Gruttadauria, J.,MacRae, I.J. (deposition date: 2018-11-19, release date: 2019-05-08, Last modification date: 2023-10-11)

Primary citation

Sheu-Gruttadauria, J.,Xiao, Y.,Gebert, L.F.,MacRae, I.J.
Beyond the seed: structural basis for supplementary microRNA targeting by human Argonaute2.
Embo J., 38:e101153-e101153, 2019

PubMed Abstract: microRNAs (miRNAs) guide Argonaute proteins to mRNAs targeted for repression. Target recognition occurs primarily through the miRNA seed region, composed of guide (g) nucleotides g2-g8. However, nucleotides beyond the seed are also important for some known miRNA-target interactions. Here, we report the structure of human Argonaute2 (Ago2) engaged with a target RNA recognized through both miRNA seed and supplementary (g13-g16) regions. Ago2 creates a "supplementary chamber" that accommodates up to five miRNA-target base pairs. Seed and supplementary chambers are adjacent to each other and can be bridged by an unstructured target loop of 1-15 nucleotides. Opening of the supplementary chamber may be constrained by tension in the miRNA 3' tail, as increases in miRNA length stabilize supplementary interactions. Contrary to previous reports, we demonstrate that optimal supplementary interactions can increase target affinity > 20-fold. These results provide a mechanism for extended miRNA targeting, suggest a function for 3' isomiRs in tuning miRNA targeting specificity, and indicate that supplementary interactions may contribute more to target recognition than is widely appreciated.

PubMed: 31268608
DOI: 10.15252/embj.2018101153

Experimental method

X-RAY DIFFRACTION (2.899 Å)