5FGO: Crystal Structure Of D. Melanogaster Pur-alpha Repeat Iii

Citation:
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.
PDB ID: 5FGODownload
MMDB ID: 135832
PDB Deposition Date: 2015/12/21
Updated in MMDB: 2016/01
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 5FGO: dimeric; determined by author and by software (PISA)
Molecular Components in 5FGO
Label Count Molecule
Proteins (2 molecules)
2
Cg1507-pb, Isoform B
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.