7KI3

Human Argonaute2:miR-122 bound to the HCV genotype 1a site-1 RNA

Summary for 7KI3

• Entry DOI: 10.2210/pdb7ki3/pdb
• Descriptor: Protein argonaute-2, miR-122, HCV genotype 1a miR-122 site-1, ... (4 entities in total)
• Functional Keywords: argonaute, mir-122, hcv, complex, hydrolase-rna complex, hydrolase/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 228672.37

Authors

Gebert, L.F.R.,MacRae, I.J. (deposition date: 2020-10-22, release date: 2021-10-06, Last modification date: 2023-10-18)

Primary citation

Gebert, L.F.R.,Law, M.,MacRae, I.J.
A structured RNA motif locks Argonaute2:miR-122 onto the 5' end of the HCV genome.
Nat Commun, 12:6836-6836, 2021

PubMed Abstract: microRNAs (miRNAs) form regulatory networks in metazoans. Viruses engage miRNA networks in numerous ways, with Flaviviridae members exploiting direct interactions of their RNA genomes with host miRNAs. For hepatitis C virus (HCV), binding of liver-abundant miR-122 stabilizes the viral RNA and regulates viral translation. Here, we investigate the structural basis for these activities, taking into consideration that miRNAs function in complex with Argonaute (Ago) proteins. The crystal structure of the Ago2:miR-122:HCV complex reveals a structured RNA motif that traps Ago2 on the viral RNA, masking its 5' end from enzymatic attack. The trapped Ago2 can recruit host factor PCBP2, implicated in viral translation, while binding of a second Ago2:miR-122 competes with PCBP2, creating a potential molecular switch for translational control. Combined results reveal a viral RNA structure that modulates Ago2:miR-122 dynamics and repurposes host proteins to generate a functional analog of the mRNA cap-binding complex.

PubMed: 34824224
DOI: 10.1038/s41467-021-27177-9

Experimental method

X-RAY DIFFRACTION (3 Å)