糖基残留的左侧构造可能会对蛋白质聚合提供保护
Purva Mishra1, Rajesh Potlia1, Kuljeet Singh Sandhu1
1DBT Bioinformatics Centre, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) -Mohali, SAS Nagar, India.
The FEBS journal
|April 17, 2025
概括
在氨基酸中独一无二的甘氨基,可以采用不允许的左撇子形状. 这些形状在进化过程中被选择,以防止蛋白质聚合并保持稳定性,有助于疾病变异预测.
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 遗传学 是一个
背景情况:
- 甘氨酸是唯一缺乏Cβ原子的氨基酸,使得独特的Ramachandran构造成为可能.
- 左撇子 (l-不允许) 构造通常被禁止用于l-氨基酸,但可用于糖.
- 糖基的l-不允许构造的功能和进化意义被低估了.
研究的目的:
- 调查糖基的l-不允许构成在蛋白质稳定性和聚合中的作用.
- 确定这些形状是否与引起疾病的遗传变异有关.
- 探索进化选择对糖基构成的压力.
主要方法:
- 在疾病和良性变异部位上对糖基的形态分析.
- 免费能量计算,以评估突变对蛋白质折叠的影响.
- 在聚合守门员地点对糖基丰富的分析,特别是在热爱动物中.
- 深度学习模型使用糖基构成特征预测致病变体.
主要成果:
- 左手糖基因在疾病变异部位上过度存在,并且在进化过程中得到了保存.
- 涉及l-不允许糖基的突变破坏了蛋白质折叠的稳定,并降低了溶解度.
- 在聚合守门人中,不允许的糖基显著丰富,特别是在热友蛋白中.
- 结合l-disallowed glycyls的深度学习模型在识别致病变体时显示出更高的准确性.
结论:
- 进化选择有利于l-不允许的糖基构成,通过控制蛋白质的稳定性和聚合来维持蛋白质静止.
- 这些发现凸显了甘氨酸在蛋白质功能中的独特形状特性的重要性.
- 这项研究提出了优先考虑与疾病相关的遗传变异和设计可溶性蛋白质的应用.
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