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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Weber, J; Bao, H; Hartlmüller, 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. 2016; 5(7): [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Madl Tobias

Dimensions Citations:

Plum Analytics:
Number of Figures: 16
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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.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Crystallography, X-Ray -
DNA, Single-Stranded - chemistry
DNA, Single-Stranded - metabolism
Drosophila -
Drosophila Proteins - chemistry
Drosophila Proteins - metabolism
Gene Deletion -
Genetic Complementation Test -
Models, Molecular -
Nucleic Acid Conformation -
Protein Binding -
Protein Conformation -
Transcription Factors - chemistry
Transcription Factors - metabolism

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