Structure and conserved RNA binding of the PAZ domain

Nature. 2003 Nov 27;426(6965):468-74. doi: 10.1038/nature02129. Epub 2003 Nov 16.


The discovery of RNA-mediated gene-silencing pathways, including RNA interference, highlights a fundamental role of short RNAs in eukaryotic gene regulation and antiviral defence. Members of the Dicer and Argonaute protein families are essential components of these RNA-silencing pathways. Notably, these two families possess an evolutionarily conserved PAZ (Piwi/Argonaute/Zwille) domain whose biochemical function is unknown. Here we report the nuclear magnetic resonance solution structure of the PAZ domain from Drosophila melanogaster Argonaute 1 (Ago1). The structure consists of a left-handed, six-stranded beta-barrel capped at one end by two alpha-helices and wrapped on one side by a distinctive appendage, which comprises a long beta-hairpin and a short alpha-helix. Using structural and biochemical analyses, we demonstrate that the PAZ domain binds a 5-nucleotide RNA with 1:1 stoichiometry. We map the RNA-binding surface to the open face of the beta-barrel, which contains amino acids conserved within the PAZ domain family, and we define the 5'-to-3' orientation of single-stranded RNA bound within that site. Furthermore, we show that PAZ domains from different human Argonaute proteins also bind RNA, establishing a conserved function for this domain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arabidopsis Proteins / chemistry*
  • Arabidopsis Proteins / metabolism*
  • Argonaute Proteins
  • Binding Sites
  • Conserved Sequence
  • Drosophila melanogaster / chemistry*
  • Evolution, Molecular
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA / metabolism*


  • AGO1 protein, Arabidopsis
  • Arabidopsis Proteins
  • Argonaute Proteins
  • RNA

Associated data

  • PDB/1R4K