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

Structure and conserved RNA binding of the PAZ domain.

Author information

1
Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, One Gustave L. Levy Place, New York, New York 10029-6574, USA.

Erratum in

  • Nature. 2004 Jan 15;427(6971):265.

Abstract

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.

PMID:
14615802
DOI:
10.1038/nature02129
[Indexed for MEDLINE]

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