Summary information and primary citation
- PDB-id
-
4w5t;
DSSR-derived features in text and
JSON formats
- Class
- hydrolase-RNA
- Method
- X-ray (2.5 Å)
- Summary
- The crystal structure of human argonaute2 bound to a
guide and target RNA containing seed pairing from 2-7
- 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.
