Recognition of 2'-O-methylated 3'-end of piRNA by the PAZ domain of a Piwi protein.
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.
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Bernd
B
Simon
John P
JP
Kirkpatrick
Stephanie
S
Eckhardt
Michael
M
Reuter
Elsa A
EA
Rocha
Miguel A
MA
Andrade-Navarro
Peter
P
Sehr
Ramesh S
RS
Pillai
Teresa
T
Carlomagno
D000595:Amino Acid Sequence; D000818:Animals; D060565:Argonaute Proteins; D001665:Binding Sites; D004251:DNA Transposable Elements; D004926:Escherichia coli; D019143:Evolution, Molecular; D020868:Gene Silencing; D008715:Methionine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D018716:Molecular Mimicry / Q000235:genetics; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020349:Surface Plasmon Resonance
D060565:Argonaute Proteins; D004251:DNA Transposable Elements; D009841:Oligonucleotides; C448522:Piwil1 protein, mouse; D011506:Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D008715:Methionine