1SI2

Crystal structure of the PAZ domain of human eIF2c1 in complex with a 9-mer siRNA-like duplex of deoxynucleotide overhang

1SI2 の概要

• エントリーDOI: 10.2210/pdb1si2/pdb
• 関連するPDBエントリー: 1SI3
• 分子名称: 5'-R(*CP*GP*UP*GP*AP*CP*U)-D(P*CP*T)-3', Eukaryotic translation initiation factor 2C 1 (3 entities in total)
• 機能のキーワード: protein-rna complex, rna interference, double helix, overhang, gene regulation-rna-dna complex, gene regulation/rna/dna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, P-body: Q9UL18
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19980.71

構造登録者

Ye, K.,Ma, J.B.,Patel, D. (登録日: 2004-02-26, 公開日: 2004-05-25, 最終更新日: 2024-02-14)

主引用文献

Ma, J.B.,Ye, K.,Patel, D.J.
Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain.
Nature, 429:318-322, 2004

PubMed Abstract: Short RNAs mediate gene silencing, a process associated with virus resistance, developmental control and heterochromatin formation in eukaryotes. RNA silencing is initiated through Dicer-mediated processing of double-stranded RNA into small interfering RNA (siRNA). The siRNA guide strand associates with the Argonaute protein in silencing effector complexes, recognizes complementary sequences and targets them for silencing. The PAZ domain is an RNA-binding module found in Argonaute and some Dicer proteins and its structure has been determined in the free state. Here, we report the 2.6 A crystal structure of the PAZ domain from human Argonaute eIF2c1 bound to both ends of a 9-mer siRNA-like duplex. In a sequence-independent manner, PAZ anchors the 2-nucleotide 3' overhang of the siRNA-like duplex within a highly conserved binding pocket, and secures the duplex by binding the 7-nucleotide phosphodiester backbone of the overhang-containing strand and capping the 5'-terminal residue of the complementary strand. On the basis of the structure and on binding assays, we propose that PAZ might serve as an siRNA-end-binding module for siRNA transfer in the RNA silencing pathway, and as an anchoring site for the 3' end of guide RNA within silencing effector complexes.

PubMed: 15152257
DOI: 10.1038/nature02519

実験手法

X-RAY DIFFRACTION (2.6 Å)