The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes.
RISC, the RNA-induced silencing complex, uses short interfering RNAs (siRNAs) or micro RNAs (miRNAs) to select its targets in a sequence-dependent manner. Key RISC components are Argonaute proteins, which contain two characteristic domains, PAZ and PIWI. PAZ is highly conserved and is found only in Argonaute proteins and Dicer. We have solved the crystal structure of the PAZ domain of Drosophila Argonaute2. The PAZ domain contains a variant of the OB fold, a module that often binds single-stranded nucleic acids. PAZ domains show low-affinity nucleic acid binding, probably interacting with the 3' ends of single-stranded regions of RNA. PAZ can bind the characteristic two-base 3' overhangs of siRNAs, indicating that although PAZ may not be a primary nucleic acid binding site in Dicer or RISC, it may contribute to the specific and productive incorporation of siRNAs and miRNAs into the RNAi pathway.
Song
Ji-Joon
JJ
Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Liu
Jidong
J
Tolia
Niraj H
NH
Schneiderman
Jonathan
J
Smith
Stephanie K
SK
Martienssen
Robert A
RA
Hannon
Gregory J
GJ
Joshua-Tor
Leemor
L
D000595:Amino Acid Sequence; D000818:Animals; D060565:Argonaute Proteins; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D004331:Drosophila melanogaster; D020868:Gene Silencing; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000737:chemistry* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D034743:RNA-Induced Silencing Complex; D011993:Recombinant Fusion Proteins; D012313:RNA