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PDB:1U04

Protein Name

Argonaute (RNA interference protein)

Species

Pyrococcus furiosus DSM 3638 (archaea, thermophile)

Biological Context

RNA degradation is one of the mechanisms developed by organisms as a means of protection from foreign RNA molecules. RNA interference (RNAi) is a mechanism involving the cleavage of RNA. RNAi is also a powerful mechanism that can be used by scientists to turn off the expression of individual genes in a cell by degrading its mRNA. RNAi is triggered by the presence of double stranded RNA which is cleaved into smaller 20 nucleotide duplex strands called small interfering RNA (siRNA) by an enzyme called Dicer. siRNA then guide the RNA-induced silencing complex (RISC) to mRNA targets for cleavage. The mRNA targets degraded are those that are complementary to the siRNA. Along with a single-strand of the siRNA, RISC also contains various other proteins. The most important among these is the Argonaute protein.

Structure Description

1u041u04_x1u04_y

The structure seen here is that of the Argonaute protein from Pyrococcus furiosus (PfAgo). Like all Argonaute proteins, PfAgo has a PIWI domain and a PIWI Argonaute Zwille (PAZ) domain. PfAgo has a crescent-shaped base consisting of the PIWI domain flanked by the N-terminal and the middle domain.The PAZ domain is held above this base by a stalk-like region located after the N-terminus. This results in a groove in the center of the base with the PAZ domain on top. Conserved residues in the PAZ domain most likely bind the 3' end of the siRNA. The core of the PIWI domain shares a conserved motif and similarity in tertiary structure with the RNase H family of enzymes, which are known to cleave single-stranded RNA guided by DNA. The conserved motif of the PIWI domain is present in the center of the groove below the PAZ domain and forms the active site. Based on these observations, the authors suggest that the Argonaute protein is the "Slicer" which cleaves the target mRNA strand whose selection is guided by the siRNA.

Protein Data Bank (PDB)

References

Source

  • Song, J.J. Smith, S.K. Hannon, G.J. Joshua-Tor, L.; "Crystal structure of Argonaute and its implications for RISC slicer activity"; Science; (2004) 305:1434-1437 PubMed:15284453.

Others

author: Ashwini Patil


Japanese version:PDB:1U04