Structural basis for piRNA 2′-O-methylated 3′-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains Journal Article

   

Authors:	Tian, Y.; Simanshu, D. K.; Ma, J. B. ; Patel, D. J.
Article Title:	Structural basis for piRNA 2′-O-methylated 3′-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains
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′-OCH3) 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′-OCH3 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′-OCH3 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′-OCH3 3′ ends.
Keywords:	unclassified drug; binding affinity; protein domain; protein binding; amino terminal sequence; crystal structure; hydrogen bond; rna structure; protein methylation; piwi interacting rna; piwi protein; hili protein; hiwi1 protein; hiwi2 protein; hiwi3 protein
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	108
Issue:	3
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	2011-01-18
Start Page:	903
End Page:	910
Language:	English
DOI:	10.1073/pnas.1017762108
PROVIDER:	scopus
PMCID:	PMC3024652
PUBMED:	21193640
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-79551634514&partnerID=40&md5=5a18f0860eb111816549442e122d0ada
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 4 March 2011" - "CODEN: PNASA" - "Source: Scopus"

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