Mechanisms of pathogenesis of missense mutations on the KDM6A-H3 interaction in type 2 Kabuki Syndrome.,Computational and Structural Biotechnology Journal

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Mechanisms of pathogenesis of missense mutations on the KDM6A-H3 interaction in type 2 Kabuki Syndrome.
Computational and Structural Biotechnology Journal ( IF 4.4 ) Pub Date : 2020-07-25 , DOI: 10.1016/j.csbj.2020.07.013
Francesco Petrizzelli _{1,

2} , Tommaso Biagini ₁ , Alessandro Barbieri _{3,

4} , Luca Parca ₁ , Noemi Panzironi ₂ , Stefano Castellana ₁ , Viviana Caputo ₂ , Angelo Luigi Vescovi ₅ , Massimo Carella ₆ , Tommaso Mazza ₁

Affiliation

Mutations in genes encoding for histone methylation proteins are associated with several developmental disorders. Among them, KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease. While nonsense mutations and short insertions/deletions are known to trigger pathogenic mechanisms, the functional effects of missense mutations are still uncharacterized. In this study, we demonstrate that a selected set of missense mutations significantly hamper the interaction between KDM6A and the histone H3, by modifying the dynamics of the linker domain, thereby causing a loss of function effect.

中文翻译：

2型歌舞伎综合症中KDM6A-H3相互作用错义突变的发病机制。

编码组蛋白甲基化蛋白的基因突变与多种发育障碍有关。其中，KDM6A是2型歌舞伎综合症的致病基因，这是一种罕见的多系统疾病。虽然已知无义突变和短插入/缺失会触发致病机制，但错义突变的功能影响仍然未知。在这项研究中，我们证明一组选定的错义突变通过改变接头结构域的动力学，显着阻碍 KDM6A 和组蛋白 H3 之间的相互作用，从而导致功能丧失效应。

更新日期：2020-07-25

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