Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex Journal Article
| Authors: | Wang, Y.; Juranek, S.; Li, H.; Sheng, G.; Tuschl, T.; Patel, D. J. |
| Article Title: | Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex |
| Abstract: | Here we report on a 3.0 Å crystal structure of a ternary complex of wild-type Thermus thermophilus argonaute bound to a 5′-phosphorylated 21-nucleotide guide DNA and a 20-nucleotide target RNA containing cleavage-preventing mismatches at the 10-11 step. The seed segment (positions 2 to 8) adopts an A-helical-like Watson-Crick paired duplex, with both ends of the guide strand anchored in the complex. An arginine, inserted between guide-strand bases 10 and 11 in the binary complex, locking it in an inactive conformation, is released on ternary complex formation. The nucleic-acid-binding channel between the PAZ- and PIWI-containing lobes of argonaute widens on formation of a more open ternary complex. The relationship of structure to function was established by determining cleavage activity of ternary complexes containing position-dependent base mismatch, bulge and 2′-O-methyl modifications. Consistent with the geometry of the ternary complex, bulges residing in the seed segments of the target, but not the guide strand, were better accommodated and their complexes were catalytically active. ©2008 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | controlled study; unclassified drug; methylation; review; protein conformation; complex formation; amino acid substitution; protein; rna interference; phosphorylation; wild type; rna; bacterial proteins; dna; geometry; substrate specificity; base sequence; base pairing; crystal structure; models, molecular; crystallography, x-ray; conformational transition; catalysis; protein structure; structure analysis; argonaute protein; rna-induced silencing complex; protein cleavage; bacterium; arginine; rna cleavage; nucleotide; chemical modification; thermus thermophilus; protein rna binding; piwi protein; nucleic acid binding protein; base pair mismatch; dna strand; dna protein complex; ternary complex factor; protein paz |
| Journal Title: | Nature |
| Volume: | 456 |
| Issue: | 7224 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2008-12-18 |
| Start Page: | 921 |
| End Page: | 926 |
| Language: | English |
| DOI: | 10.1038/nature07666 |
| PUBMED: | 19092929 |
| PROVIDER: | scopus |
| PMCID: | PMC2765400 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 98" - "Export Date: 17 November 2011" - "CODEN: NATUA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work