8CHT

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

8CHT の概要

• エントリーDOI: 10.2210/pdb8cht/pdb
• 分子名称: Transcriptional activator protein Pur-alpha, ACETATE ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: rna/dna binding, pur repeat, pc4-like fold, rna binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 71211.57

構造登録者

Janowski, R.,Niessing, D. (登録日: 2023-02-08, 公開日: 2024-02-21, 最終更新日: 2024-05-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.95 Å)