3O6E

Crystal Structure of human Hiwi1 PAZ domain (residues 277-399) in complex with 14-mer RNA (12-bp + 2-nt overhang) containing 2'-OCH3 at its 3'-end

Summary for 3O6E

• Entry DOI: 10.2210/pdb3o6e/pdb
• Related: 3O3I 3O7V 3O7X
• Descriptor: Piwi-like protein 1, RNA (5'-R(*GP*CP*GP*AP*AP*UP*AP*UP*UP*CP*GP*CP*UP*(OMU))-3') (3 entities in total)
• Functional Keywords: piwi, paz, rna silencing, pi-rna, hiwi1, hili, paz domain, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : Q96J94
• Total number of polymer chains: 2
• Total formula weight: 19063.87

Authors

Tian, Y.,Simanshu, D.K.,Ma, J.-B.,Patel, D.J. (deposition date: 2010-07-28, release date: 2011-01-12, Last modification date: 2024-11-20)

Primary citation

Tian, Y.,Simanshu, D.K.,Ma, J.B.,Patel, D.J.
Inaugural Article: Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains.
Proc.Natl.Acad.Sci.USA, 108:903-910, 2011

PubMed Abstract: Argonaute and Piwi proteins are key players in the RNA silencing pathway, with the former interacting with micro-RNAs (miRNAs) and siRNAs, whereas the latter targets piwi-interacting RNAs (piRNAs) that are 2'-O-methylated (2(')-OCH(3)) at their 3' ends. Germline-specific piRNAs and Piwi proteins play a critical role in genome defense against transposable elements, thereby protecting the genome against transposon-induced defects in gametogenesis and fertility. Humans contain four Piwi family proteins designated Hiwi1, Hiwi2, Hiwi3, and Hili. We report on the structures of Hili-PAZ (Piwi/Argonaute/Zwille) domain in the free state and Hiwi1 PAZ domain bound to self-complementary 14-mer RNAs (12-bp + 2-nt overhang) containing 2(')-OCH(3) and 2'-OH at their 3' ends. These structures explain the molecular basis underlying accommodation of the 2(')-OCH(3) group within a preformed Hiwi1 PAZ domain binding pocket, whose hydrophobic characteristics account for the preferential binding of 2(')-OCH(3) over 2'-OH 3' ends. These results contrast with the more restricted binding pocket for the human Ago1 PAZ domain, which exhibits a reverse order, with preferential binding of 2'-OH over 2(')-OCH(3) 3' ends.

PubMed: 21193640
DOI: 10.1073/pnas.1017762108

Experimental method

X-RAY DIFFRACTION (2.904 Å)