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使用基于AlphaFold 2预测的结构建模,对TMEM165变异的致病性进行了新的洞察

Dominique Legrand¹, Mélissandre Herbaut¹, Zoé Durin¹

¹Univ. Lille, CNRS, UMR 8576 - UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France.

Computational and structural biotechnology journal

|July 7, 2023

概括

TMEM165突变通过扰乱运输,导致先天性糖基化乱. 一个新的3D模型解释了这些突变,即使是遥远的突变,如何影响蛋白质功能和Mn2+运输,这对糖化至关重要.

科学领域:

生物化学生物化学
结构生物学结构生物学
遗传学是一个遗传学.

背景情况:

TMEM165是一种高尔基蛋白,对 (Mn2+) 运输至关重要,对糖化酶至关重要.
TMEM165中的突变会导致先天性糖基化乱 (CDG),影响患者的健康.
以前的拓预测未能澄清TMEM165的结构和突变效应.

研究的目的:

使用先进的建模技术,阐明TMEM165的3D结构.
了解患者衍生和实验突变如何影响TMEM165功能.
为Mn2+运输及其在糖化中的作用提供结构基础.

主要方法:

在最初的TMEM165模型构建中使用AlphaFold 2.
通过使用脂质和水的分子动力学模拟来完善模型.
分析了保存模式和特定突变的结构影响,如G>R304.4.

主要成果:

开发了一个精细的TMEM165的3D模型,揭示了双重重复结构.
鉴定出一个被假定的Mn2+结合点,该结合点是由细胞质侧保留的动图形成的.
解释了G>R304突变和其他突变对TMEM165传输的功能影响.

结论:

3D TMEM165模型提供了对Mn2+运输机制和CDG病原体的洞察.
结构理解有助于解释突变对TMEM165功能的影响.
该模型为TMEM165与CaCA2/UPF0016家族和Lyse超级家族中的相关载体进行比较提供了基础.

关键词:

这是CDG的CDG.葡萄糖基酶化是指葡萄糖基酶化的过程.是一种.建模建模模型是什么在TEMEM165中,我们可以看到TEMEM165.

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