5FGO

Crystal structure of D. melanogaster Pur-alpha repeat III.

5FGO の概要

• エントリーDOI: 10.2210/pdb5fgo/pdb
• 分子名称: CG1507-PB, isoform B, CHLORIDE ION (3 entities in total)
• 機能のキーワード: dna-protein interaction, rna-protein interaction, dna unwinding, fxtas, als, ftld, 5q31.3 microdeletion syndrome, neurodegeneration, dna binding protein
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 58262.00

構造登録者

Windhager, A.,Janowski, R.,Niessing, D. (登録日: 2015-12-21, 公開日: 2016-01-20, 最終更新日: 2024-11-20)

主引用文献

Weber, J.,Bao, H.,Hartlmuller, C.,Wang, Z.,Windhager, A.,Janowski, R.,Madl, T.,Jin, P.,Niessing, D.
Structural basis of nucleic-acid recognition and double-strand unwinding by the essential neuronal protein Pur-alpha.
Elife, 5:-, 2016

PubMed Abstract: The neuronal DNA-/RNA-binding protein Pur-alpha is a transcription regulator and core factor for mRNA localization. Pur-alpha-deficient mice die after birth with pleiotropic neuronal defects. Here, we report the crystal structure of the DNA-/RNA-binding domain of Pur-alpha in complex with ssDNA. It reveals base-specific recognition and offers a molecular explanation for the effect of point mutations in the 5q31.3 microdeletion syndrome. Consistent with the crystal structure, biochemical and NMR data indicate that Pur-alpha binds DNA and RNA in the same way, suggesting binding modes for tri- and hexanucleotide-repeat RNAs in two neurodegenerative RNAopathies. Additionally, structure-based in vitro experiments resolved the molecular mechanism of Pur-alpha's unwindase activity. Complementing in vivo analyses in Drosophila demonstrated the importance of a highly conserved phenylalanine for Pur-alpha's unwinding and neuroprotective function. By uncovering the molecular mechanisms of nucleic-acid binding, this study contributes to understanding the cellular role of Pur-alpha and its implications in neurodegenerative diseases.

PubMed: 26744780
DOI: 10.7554/eLife.11297

実験手法

X-RAY DIFFRACTION (2.6 Å)