4DNN

Crystal structure of the Quaking Qua1 homodimerization domain

4DNN の概要

• エントリーDOI: 10.2210/pdb4dnn/pdb
• 分子名称: Protein quaking, CALCIUM ION (3 entities in total)
• 機能のキーワード: helix-turn-helix, hydrophobic homodimer interface, perpendicular stacking of protomers, developmental protein, rna-binding, splicing, translation regulation
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm. Isoform 1: Cytoplasm. Isoform 3: Cytoplasm. Isoform 4: Cytoplasm: Q9QYS9
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13419.94

構造登録者

Beuck, C.,Qu, S.,Williamson, J.R. (登録日: 2012-02-08, 公開日: 2012-09-12, 最終更新日: 2024-11-06)

主引用文献

Beuck, C.,Qu, S.,Fagg, W.S.,Ares, M.,Williamson, J.R.
Structural Analysis of the Quaking Homodimerization Interface.
J.Mol.Biol., 423:766-781, 2012

PubMed Abstract: Quaking (QkI) is a prototypical member of the STAR (signal transducer and activator of RNA) protein family, which plays key roles in posttranscriptional gene regulation by controlling mRNA translation, stability and splicing. QkI-5 has been shown to regulate mRNA expression in the central nervous system, but little is known about its roles in other tissues. STAR proteins function as dimers and bind to bipartite RNA sequences; however, the structural and functional roles of homodimerization and heterodimerization are still unclear. Here, we present the crystal structure of the QkI dimerization domain, which adopts a similar stacked helix-turn-helix arrangement as its homologs GLD-1 (germ line development defective-1) and Sam68 (Src-associated protein during mitosis, 68kDa) but differs by an additional helix inserted in the dimer interface. Variability of the dimer interface residues likely ensures selective homodimerization by preventing association with non-cognate STAR family proteins in the cell. Mutations that inhibit dimerization also significantly impair RNA binding in vitro, alter QkI-5 protein levels and impair QkI function in a splicing assay in vivo. Together, our results indicate that a functional Qua1 homodimerization domain is required for QkI-5 function in mammalian cells.

PubMed: 22982292
DOI: 10.1016/j.jmb.2012.08.027

実験手法

X-RAY DIFFRACTION (2.1 Å)