4Z4I: Human Argonaute2 A481t Mutant Bound To T1-g Target Rna

Citation:
Abstract
MicroRNAs (miRNAs) direct post-transcriptional regulation of human genes by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. An enigmatic feature of many conserved mammalian miRNA target sites is that an adenosine (A) nucleotide opposite miRNA nucleotide-1 confers enhanced target repression independently of base pairing potential to the miRNA. In this study, we show that human Argonaute2 (Ago2) possesses a solvated surface pocket that specifically binds adenine nucleobases in the 1 position (t1) of target RNAs. t1A nucleotides are recognized indirectly through a hydrogen-bonding network of water molecules that preferentially interacts with the N6 amine on adenine. t1A nucleotides are not utilized during the initial binding of Ago2 to its target, but instead function by increasing the dwell time on target RNA. We also show that N6 adenosine methylation blocks t1A recognition, revealing a possible mechanism for modulation of miRNA target site potency.
PDB ID: 4Z4IDownload
MMDB ID: 132867
PDB Deposition Date: 2015/4/2
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4Z4I: trimeric; determined by author and by software (PISA)
Molecular Components in 4Z4I
Label Count Molecule
Protein (1 molecule)
1
Protein Argonaute-2(Gene symbol: AGO2)
Molecule annotation
Nucleotides(2 molecules)
1
RNA (5'- R(p*up*up*cp*ap*cp*ap*up*up*gp*cp*cp*cp*ap*ap*gp*up*cp*up*up*u)-3')
Molecule annotation
1
RNA (5'-r(*cp*ap*ap*up*gp*up*gp*a)-3')
Molecule annotation
Chemicals (6 molecules)
1
3
2
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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