氨酸无处置驱动罗多普辛蛋白的营业额
Allen P F Chen1, Leon Chea2,3,4, Eun-Jin Lee2,3,4,5
1Medical Scientist Training Program, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
Advances in experimental medicine and biology
|July 13, 2023
概括
罗多素P23H上的氨酸残留物对其无处不在和降解至关重要. 突变这些溶酶减缓了蛋白质的循环,为自身主导性视网膜炎提供了洞察力.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生化学
背景情况:
- 罗多普辛是棒光受体中的关键G蛋白结合受体.
- 罗多普辛的150多个突变导致自体主导视网膜色素炎 (adRP).
- 罗多素P23H突变是美国adRP的常见原因,导致错误折叠的蛋白质降解.
研究的目的:
- 调查氨酸残留在P23H罗多素无处不在和营业额中的作用.
- 确定氨酸无处不在是否是P23H罗多素降解的关键机制.
主要方法:
- HEK293细胞被感染了野生类型和P23H rhodopsin结构.
- 罗多素P23H中的氨酸残留物被突变为氨酸 (K-null P23H).
- 分析了ubiquitylation水平和蛋白质周转率 (使用循环胺追逐).
主要成果:
- 与完整的P23H rhodopsin相比,K-null P23H rhodopsin显示出明显减少的无处不在.
- 与P23H rhodopsin相比,K-null的P23H蛋白循环速度显著较慢.
- 野生类型的罗多普辛与所有 lysines 突变为 arginine 也表现出减少的无处不在.
结论:
- 氨酸残留的泛基化是P23H罗多素降解的一个关键的翻译后修改.
- 向氨酸无处不在可能为P23H rhodopsin相关的adRP.提供治疗策略.
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