A potential protein-RNA recognition event along the RISC-loading pathway from the structure of A. aeolicus Argonaute with externally bound siRNA Journal Article

   

Authors:	Yuan, Y. R.; Pei, Y.; Chen, H. Y.; Tuschl, T.; Patel, D. J.
Article Title:	A potential protein-RNA recognition event along the RISC-loading pathway from the structure of A. aeolicus Argonaute with externally bound siRNA
Abstract:	Argonaute proteins are key components of the RNA-induced silencing complex (RISC). They provide both architectural and catalytic functionalities associated with small interfering RNA (siRNA) guide strand recognition and subsequent guide strand-mediated cleavage of complementary mRNAs. We report on the 3.0 Å crystal structures of 22-mer and 26-mer siRNAs bound to Aquifex aeolicus Argonaute (Aa-Ago), where one 2 nt 3′ overhang of the siRNA inserts into a cavity positioned on the outer surface of the PAZ-containing lobe of the bilobal Aa-Ago architecture. The first overhang nucleotide stacks over a tyrosine ring, while the second overhang nucleotide, together with the intervening sugar-phosphate backbone, inserts into a preformed surface cavity. Photochemical crosslinking studies on Aa-Ago with 5-iodoU-labeled single-stranded siRNA and siRNA duplex provide support for this externally bound siRNA-Aa-Ago complex. The structure and biochemical data together provide insights into a protein-RNA recognition event potentially associated with the RISC-loading pathway. © 2006 Elsevier Ltd. All rights reserved.
Keywords:	signal transduction; controlled study; mutation; nonhuman; small interfering rna; rna, small interfering; rna interference; rna; crystal structure; models, molecular; binding sites; nucleic acid conformation; rna structure; crystallization; structure analysis; phosphate; rna induced silencing complex; rna, double-stranded; nucleotide; sugar; protein rna binding; endoribonucleases; cross linking; single stranded rna; aquifex aeolicus
Journal Title:	Structure
Volume:	14
Issue:	10
ISSN:	0969-2126
Publisher:	Cell Press
Date Published:	2006-10-01
Start Page:	1557
End Page:	1565
Language:	English
DOI:	10.1016/j.str.2006.08.009
PUBMED:	17027504
PROVIDER:	scopus
PMCID:	PMC4692372
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33749244630&partnerID=40&md5=48c3033060327f8e3a6179d8eddd01a5
Notes:	--- - "Cited By (since 1996): 20" - "Export Date: 4 June 2012" - "CODEN: STRUE" - "Source: Scopus"

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