Argonaute: Difference between revisions

<scene name='Argonaute/Ago2-piwi/1'>The larger Piwi domain</scene> (~300 aminoacids) is found in a large number of related nucleic-acid binding proteins, in particular those involved in RNA binding and cleavage. In the Argonaute protein, its function is the dsRNA guided hydrolysis of ssRNA <ref name='ref6'>15800637</ref>. PIWI is structurally an RNase H domain, and in Argonaute it servers as the 'Slicer', or the component responsible for cleaving the mRNA in the RISC complex <ref name='ref6'>pmid 15284453</ref>. Predictions point to <scene name='Argonaute/Ago2-piwi-mg/1'>a putative binding site</scene> for magnesium bivalent cations. However, in contrast to the findings in prokaryotic enzymes, eukaryotic structures were found lacking the metal <ref name='ref1'/>.

The majority of the RNA binding residues are located in the PIWI domain. The RNA molecule is bound in a conformation similar to DNA molecules in prokaryotic structures. The fact that the RNA bases 1 to 7 are well-defined in the electron density map hint at an uniform conformation of this region, perhaps forced by the protein. <scene name='Argonaute/Ago2-y529/5'>The 5' base of the RNA molecule interacts</scene> with Y529 through base-stacking, along with hydrogen bonds to this same tyrosine residue, K533, N545 and K566. <scene name='Argonaute/Ago2-water/4'>Water mediates a couple of hydrogen bonds</scene> between the 5' phosphate and K570, R812 and the carboxyl group of A859. As such, the majority of the interactions between Argonaute and the RNA molecule are electrostatic in nature, arising from hydrogen bonding and salt bridges to the phosphate backbone. Van der Waals interactions between the ribose sugar ring and protein residues also contribute to the overall stabilization of the interaction. Residues S220, R357, R714 and R761 of the MID domain, together with a part of the PIWI domain bind the bases 7-9 <ref name='ref1'/>.