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Publication Abstract from PubMed

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.

Structural basis of nucleic-acid recognition and double-strand unwinding by the essential neuronal protein Pur-alpha.,Weber J, Bao H, Hartlmuller C, Wang Z, Windhager A, Janowski R, Madl T, Jin P, Niessing D Elife. 2016 Jan 8;5. pii: e11297. doi: 10.7554/eLife.11297. PMID:26744780^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.