SNAP output for PDB entry 5fgp [SNAP web server]

PDB-id

5fgp; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein

Method

X-ray (2.0 Å)

Summary

Crystal structure of d. melanogaster pur-alpha repeat i-ii in complex with DNA.

Reference

Weber J, Bao H, Hartlmuller C, Wang Z, Windhager A, Janowski R, Madl T, Jin P, Niessing D (2016): "Structural basis of nucleic-acid recognition and double-strand unwinding by the essential neuronal protein Pur-alpha." Elife, 5. doi: 10.7554/eLife.11297.

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.