Recognition of 2'-O-methylated 3'-end of piRNA by the PAZ domain of a Piwi protein

  • Structure. 2011 Feb 9;19(2):172-80. doi: 10.1016/j.str.2010.11.015.
Bernd Simon  1 ,  John P Kirkpatrick ,  Stephanie Eckhardt ,  Michael Reuter ,  Elsa A Rocha ,  Miguel A Andrade-Navarro ,  Peter Sehr ,  Ramesh S Pillai ,  Teresa Carlomagno
Affiliations
  • 1. Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
PMID: 21237665 DOI: 10.1016/j.str.2010.11.015
Abstract

Piwi proteins are germline-specific Argonautes that associate with small RNAs called Piwi-interacting RNAs (piRNAs), and together with these RNAs are implicated in transposon silencing. The PAZ domain of Argonaute proteins recognizes the 3'-end of the RNA, which in the case of piRNAs is invariably modified with a 2'-O-methyl group. Here, we present the solution structure of the PAZ domain from the mouse Piwi protein, MIWI, in complex with an 8-mer piRNA mimic. The methyl group is positioned in a hydrophobic cavity made of conserved Amino acids from strand β7 and helix α3, where it is contacted by the side chain of methionine-382. Our structure is similar to that of Ago-PAZ, but subtle differences illustrate how the PAZ domain has evolved to accommodate distinct 3' ends from a variety of RNA substrates.