9E2C
Crystal structure of DEAD-box RNA helicase DDX3X R326H mutant
Summary for 9E2C
| Entry DOI | 10.2210/pdb9e2c/pdb |
| Descriptor | Isoform 2 of ATP-dependent RNA helicase DDX3X, GLYCEROL (3 entities in total) |
| Functional Keywords | dead-box rna helicase, rna binding protein, liquid-liquid phase separation |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 56164.46 |
| Authors | Prado, P.F.V.,Oliveira, J.F.,Nascimento, A.F.Z. (deposition date: 2024-10-22, release date: 2025-10-29, Last modification date: 2026-05-13) |
| Primary citation | 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 Cited by 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: 41875230DOI: 10.1126/scisignal.adv4376 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
Download full validation report
