SNAP output for PDB entry 4w5o [SNAP web server]

PDB-id

4w5o; SNAP-derived features in text and JSON formats; DNAproDB

Class

hydrolase-RNA

Method

X-ray (1.802 Å)

Summary

The crystal structure of human argonaute2 bound to a guide and target RNA containing seed pairing from 2-9

Reference

Schirle NT, Sheu-Gruttadauria J, MacRae IJ (2014): "Gene regulation. Structural basis for microRNA targeting." Science, 346, 608-613. doi: 10.1126/science.1258040.

Abstract

MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. We determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions with the guide-target minor groove allow Ago2 to interrogate target RNAs in a sequence-independent manner, whereas an adenosine binding-pocket opposite guide nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is avoided through an inhibitory coordination of one catalytic magnesium ion. These results explain the conserved nucleotide-pairing patterns in animal miRNA target sites first observed over two decades ago.