9/13/2023 0 Comments Download nucleic acid structureA technique called X-ray crystallography was then used to determine the three-dimensional structure of the Pur-alpha/DNA complex in fine enough detail to work out the position of individual atoms.īased on this structure, Weber et al. obtained Pur-alpha from the fruit fly and crystallized the protein bound to DNA. Other questions also remained unanswered: how does Pur-alpha recognize DNA and RNA? Does the loss of Pur-alpha’s binding to DNA and RNA contribute to neurodegenerative diseases? But it was not clear how this DNA unwinding occurs, and the biological significance of this activity was unknown. One example is the Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), which causes memory and movement problems.Įxperiments with isolated proteins and double-stranded DNA show that Pur-alpha is able to separate the two DNA strands. In humans, there are several neurodegenerative diseases in which Pur-alpha is involved. It also binds to RNA molecules, which are copies of a gene, and helps to distribute them within the neuron. For example, Pur-alpha can bind to DNA to regulate gene activity. This is the case for a protein called Pur-alpha, which is essential for neurons to work correctly. Some proteins perform several different tasks inside cells. 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. Complementing in vivo analyses in Drosophila demonstrated the importance of a highly conserved phenylalanine for Pur-alpha's unwinding and neuroprotective function. Additionally, structure-based in vitro experiments resolved the molecular mechanism of Pur-alpha's unwindase activity. 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. It reveals base-specific recognition and offers a molecular explanation for the effect of point mutations in the 5q31.3 microdeletion syndrome. Here, we report the crystal structure of the DNA-/RNA-binding domain of Pur-alpha in complex with ssDNA. Pur-alpha-deficient mice die after birth with pleiotropic neuronal defects. The neuronal DNA-/RNA-binding protein Pur-alpha is a transcription regulator and core factor for mRNA localization.
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