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Structure and conserved RNA binding of the PAZ domain

Structure and conserved RNA binding of the PAZ domain The discovery of RNA-mediated gene-silencing pathways, including RNA interference 1,2,3 , highlights a fundamental role of short RNAs in eukaryotic gene regulation 4,5,6,7,8,9,10 and antiviral defence 11,12 . Members of the Dicer and Argonaute protein families are essential components of these RNA-silencing pathways 13,14,15,16,17,18,19 . 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 β-barrel capped at one end by two α-helices and wrapped on one side by a distinctive appendage, which comprises a long β-hairpin and a short α-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 β-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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

Structure and conserved RNA binding of the PAZ domain

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References (33)

Publisher
Springer Journals
Copyright
Copyright © 2003 by Macmillan Magazines Ltd.
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/nature02129
Publisher site
See Article on Publisher Site

Abstract

The discovery of RNA-mediated gene-silencing pathways, including RNA interference 1,2,3 , highlights a fundamental role of short RNAs in eukaryotic gene regulation 4,5,6,7,8,9,10 and antiviral defence 11,12 . Members of the Dicer and Argonaute protein families are essential components of these RNA-silencing pathways 13,14,15,16,17,18,19 . 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 β-barrel capped at one end by two α-helices and wrapped on one side by a distinctive appendage, which comprises a long β-hairpin and a short α-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 β-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.

Journal

Nature – Springer Journals

Published: Nov 16, 2003

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