Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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):
Doi: 10.7554/eLife.11297
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Madl Tobias
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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.
- 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