8CHT

Crystal structure of human PURA (fragment Glu57-Glu212, PUR repeat I and II)

Summary for 8CHT

• Entry DOI: 10.2210/pdb8cht/pdb
• Descriptor: Transcriptional activator protein Pur-alpha, ACETATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: rna/dna binding, pur repeat, pc4-like fold, rna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 71211.57

Authors

Janowski, R.,Niessing, D. (deposition date: 2023-02-08, release date: 2024-02-21, Last modification date: 2024-05-08)

Primary citation

Proske, M.,Janowski, R.,Bacher, S.,Kang, H.S.,Monecke, T.,Koehler, T.,Hutten, S.,Tretter, J.,Crois, A.,Molitor, L.,Varela-Rial, A.,Fino, R.,Donati, E.,De Fabritiis, G.,Dormann, D.,Sattler, M.,Niessing, D.
PURA syndrome-causing mutations impair PUR-domain integrity and affect P-body association.
Elife, 13:-, 2024

PubMed Abstract: Mutations in the human gene cause the neurodevelopmental PURA syndrome. In contrast to several other monogenetic disorders, almost all reported mutations in this nucleic acid-binding protein result in the full disease penetrance. In this study, we observed that patient mutations across PURA impair its previously reported co-localization with processing bodies. These mutations either destroyed the folding integrity, RNA binding, or dimerization of PURA. We also solved the crystal structures of the N- and C-terminal PUR domains of human PURA and combined them with molecular dynamics simulations and nuclear magnetic resonance measurements. The observed unusually high dynamics and structural promiscuity of PURA indicated that this protein is particularly susceptible to mutations impairing its structural integrity. It offers an explanation why even conservative mutations across PURA result in the full penetrance of symptoms in patients with PURA syndrome.

PubMed: 38655849
DOI: 10.7554/eLife.93561

Experimental method

X-RAY DIFFRACTION (1.95 Å)