| Autor: |
Matheus de Castro Fonseca, Juliana Ferreira de Oliveira, Bruno Henrique Silva Araujo, Camila Canateli, Paula Favoretti Vital do Prado, Dionísio Pedro Amorim Neto, Beatriz Pelegrini Bosque, Paulla Vieira Rodrigues, João Vitor Pereira de Godoy, Katiane Tostes, Helder Veras Ribeiro Filho, Andrey Fabricio Ziem Nascimento, Angela Saito, Celisa Caldana Costa Tonoli, Fernanda Aparecida Heleno Batista, Paulo Sergio Lopes de Oliveira, Ana Carolina Figueira, Silvia Souza da Costa, Ana Cristina Victorino Krepischi, Carla Rosenberg, Harry Westfahl, Jr., Antônio José Roque da Silva, Kleber Gomes Franchini |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 24, Iss 8, Pp 102841- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2021.102841 |
| Popis: |
Summary: Current studies estimate that 1–3% of females with unexplained intellectual disability (ID) present de novo splice site, nonsense, frameshift, or missense mutations in the DDX3X protein (DEAD-Box Helicase 3 X-Linked). However, the cellular and molecular mechanisms by which DDX3X mutations impair brain development are not fully comprehended. Here, we show that the ID-linked missense mutation L556S renders DDX3X prone to aggregation. By using a combination of biophysical assays and imaging approaches, we demonstrate that this mutant assembles solid-like condensates and amyloid-like fibrils. Although we observed greatly reduced expression of the mutant allele in a patient who exhibits skewed X inactivation, this appears to be enough to sequestrate healthy proteins into solid-like ectopic granules, compromising cell function. Therefore, our data suggest ID-linked DDX3X L556S mutation as a disorder arising from protein misfolding and aggregation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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