Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex (Nature, 2008, 456:921-926)

報告日期: 2009/03/20
報告時間: 15:10/16:00
報告學生: Rasmani Hazra (因故取消)
講評老師: 王淑鶯
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980320-1.pdf

Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex

 

             Yanli Wang, Stefan Juranek, Haitao Li, Gang Sheng, Thomas Tuschl  & Dinshaw J. Patel

 

                                                            Nature 456, 921-927 (2008)

 

Speaker: Rasmani Hazra

Commentator: Prof. Wang, Shu-Ying

Date: March 20, 2009

Time: 15:10 – 16:00

Place: Room No. 602

 

Abstract:

The Argonaute protein family was first identified in plants, and members are defined by the presence of PAZ (Piwi-Argonaute-Zwille) and PIWI domains. Argonaute proteins are highly conserved between species and many organisms encode multiple members of the family. Argonaute proteins and small interfering RNAs (siRNAs) are the known signature components of the RNA interference effector complex RNA-induced silencing complex (RISC). Some Ago proteins with active endonuclease domains contribute to the maturation of bound short interfering RNAs (siRNAs) by degradative cleavage of the passenger strand and subsequent guide-strand-mediated sequence specific cleavage of target RNAs. Here, the authors report on a 3.0 angstrom crystal structure of a ternary complex of wild-type Thermus thermophilus argonaute bound to a 59-phosphorylated 21-nucleotide guide DNA and a 20-nucleotide target RNA containing cleavage-preventing mismatches at the 10-11 step. The bases of the guide DNA can be traced for the 1-10 segments, in which the 59- phosphate is inserted into its binding pocket in the mid domain and can be traced for the 18/19 to 21 segments, in which nucleotides 20 and 21 at the 39 end are inserted into their binding pocket in the PAZ domain. The nucleic-acid-binding channel between the PAZ- and PIWI-containing lobes of argonaute widens on formation of a more open ternary complex. The structural results on the ternary Ago complex have highlighted details of guide-strand-mediated target RNA recognition spanning the seed segment, and the conformational transitions that expand the nucleic-acid-binding channel within the bilobal Ago scaffold, thereby accommodating and aligning the target RNA for eventual site-specific cleavage. The relationship of structure of function emphasize that Piwi and Ago scaffolds have sufficient plasticity to accommodate different length guide strands, and that the size range of naturally accommodated small RNA classes are a direct consequence of their distinct biogenesis mechanisms.

 

References:

1.     Yanli, W., Stefan, J., Haitao, L., Gang, S., Thomas, T., & Dinshaw, JP. Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature 456, 921-926 (2008).

2.     Song, JJ., Smith, SK., Hannon, GJ., & Joshua-Tor, L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305, 1434-1437 (2004).