9E2C

Crystal structure of DEAD-box RNA helicase DDX3X R326H mutant

9E2C の概要

• エントリーDOI: 10.2210/pdb9e2c/pdb
• 分子名称: Isoform 2 of ATP-dependent RNA helicase DDX3X, GLYCEROL (3 entities in total)
• 機能のキーワード: dead-box rna helicase, rna binding protein, liquid-liquid phase separation
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 56164.46

構造登録者

Prado, P.F.V.,Oliveira, J.F.,Nascimento, A.F.Z. (登録日: 2024-10-22, 公開日: 2025-10-29, 最終更新日: 2026-05-13)

主引用文献

Rosa E Silva, I.,do Prado, P.F.V.,Benevenutti, F.Z.,de Oliveira, R.R.,Passos, A.R.,Canateli, C.,Messias, I.G.,Trindade, D.M.,Bortot, L.O.,Guerra, J.V.S.,Hancio, T.,Sforca, M.L.,Nascimento, A.F.Z.,Mercaldi, G.F.,Pereira, J.G.C.,Fonseca, M.C.,de Oliveira, P.S.L.,de Carvalho, M.,Smetana, J.H.C.,Krepischi, A.C.V.,Franchini, K.G.,de Oliveira, J.F.
DDX3X is a Cl - -sensitive RNA helicase.
Sci.Signal., 19:eadv4376-eadv4376, 2026

PubMed Abstract: Cl homeostasis is pivotal during neurodevelopment and in multiple processes in mature neurons, and its disruption is implicated in several neurodevelopmental disorders. Here, we investigated the role of Cl in regulating DDX3X, an ATP-dependent RNA helicase that is associated with a neurodevelopmental disorder and is involved in stress granule assembly through biomolecular condensation. Cl directly interacted with the DDX3X helicase core in the RNA binding region. This interaction impaired both ATPase and RNA helicase activities at physiologically relevant concentrations in a manner similar to inorganic phosphate and disrupted its condensation propensity in vitro. In neuroblastoma cells, Cl efflux induced the formation of large, persistent DDX3X-containing stress granules. Furthermore, the R326H mutation, which is linked to a severe neurodevelopmental disorder, altered the chemical environment of the Cl-binding site and impaired Cl-sensitive functions. Together, our findings demonstrate that Cl binding regulates DDX3X functions and provide insights into the molecular pathophysiology of a neurodevelopmental disorder-linked mutation in DDX3X.

PubMed: 41875230
DOI: 10.1126/scisignal.adv4376

実験手法

X-RAY DIFFRACTION (2.3 Å)