structure and nucleic-acid binding of the drosophila argonaute 2 paz domain

Structure and nucleic-acid binding of the DrosophilaArgonaute 2 PAZ domain

Andreas Lingel, Bernd Simon, Elisa Izaurralde & Michael Sattler

European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany

Nature. 2003 Nov 27;426(6965):465-9

指導老師 :鄒文雄主講人 :蔡榮育

11/26/2004

The siRNA pathway

View structure

Ribbon representation of the Ago2 PAZ domain

Biological question

• The Argonaute 2 protein (Ago2) is a critical component of RISC. Both Argonaute and Dicer family proteins contain a common PAZ domain whose function is unknown.

(1) What is the function of the PAZ domain?

(2) Which residue is important?

Surface representation of the PAZ domain

Nucleic-acid binding activity of the Ago2 PAZ

domain

Result• The RNA-binding region involves highly

conserved residues, specifically Arg 55 (β 2), Phe 72 (β 3), Thr 80 (β 4), Val 102 (β 5) and Ile 81 (α 3), but also the less conserved Phe 50 in the β 1–β 2 loop.

• The results identify Phe 50 and Phe 72 as critical residues for RNA binding.

• The PAZ domain also binds single-stranded or double-stranded DNA.

問題探討• PAZ domain 除了 Phe50 和 Phe72 外 , 還

有哪些 residues 與 RNA 結合 ? 這些 residues 之特性為何 ?

• BLAST 結果呈兩極化 , 可能之原因為何 ?

• Alignment 結果中其他 conserved residues 可能扮演的角色 ?

BLAST

Alignment