4W5Q

The Crystal Structure of Human Argonaute2 Bound to a Guide and Target RNA Containing Seed Pairing from 2-8

Summary for 4W5Q

• Entry DOI: 10.2210/pdb4w5q/pdb
• Related: 4W5N 4W5O 4W5R 4W5T
• Descriptor: Protein argonaute-2, RNA (5'-R(P*UP*UP*CP*AP*CP*AP*UP*UP*GP*CP*CP*CP*AP*AP*GP*UP*CP*U)-3'), RNA (5'-R(*AP*AP*AP*UP*GP*UP*GP*AP*AP*A)-3'), ... (5 entities in total)
• Functional Keywords: ago2, guide, target, rnase, rnai, hydrolase-rna complex, hydrolase/rna
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm, P-body : Q9UKV8
• Total number of polymer chains: 3
• Total formula weight: 107937.64

Authors

Schirle, N.T.,MacRae, I.J. (deposition date: 2014-08-18, release date: 2014-11-12, Last modification date: 2023-09-27)

Primary citation

Schirle, N.T.,Sheu-Gruttadauria, J.,MacRae, I.J.
Gene regulation. Structural basis for microRNA targeting.
Science, 346:608-613, 2014

PubMed 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.

PubMed: 25359968
DOI: 10.1126/science.1258040

Experimental method

X-RAY DIFFRACTION (3.101 Å)