氨酸硫氧化物减少酶和胆固醇运输体STARD3构成了有效的胆固醇氧化物排毒系统
Jung Mi Lim1, Venkata R Sabbasani2, Rolf E Swenson2
1Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
The Journal of biological chemistry
|July 28, 2023
概括
胆固醇运输蛋白 STARD3 结合 metionin硫氧化减少酶 (MSR) 并通过胆固醇氧化物进行氧化. MSRs减少氧化氨酸残留物,保护细胞免受毒性.
科学领域:
- 细胞氧化应激和防御机制.
- 胆固醇的新陈代谢和运输.
- 酶学和蛋白质功能.
背景情况:
- 氨酸硫氧化还原酶 (MSRs) 对于细胞防御对反应性氧物种至关重要.
- STARD3 是一种胆固醇运输蛋白,以前发现它能结合甲二硫酸减少酶A (MSRA).
- 蛋白质中的氧化氨酸残留物可能会损害功能并导致细胞损伤.
研究的目的:
- 研究STARD3和其他MSR酶 (MSRB家族) 之间的相互作用.
- 为了确定STARD3是否与胆固醇氧化物结合,以及其氨酸残留物是否被氧化.
- 阐明STARD3氨酸氧化在胆固醇氧化物排毒中的作用.
主要方法:
- 生物化学分析证实STARD3与MSRA和MSRB酶结合.
- 化STARD3与胆固醇氧化的特定位置异构体.
- 在STARD3.3.上进行质谱测量以识别氧化氨酸残留物 (Met307和Met427).
- 评估STARD3在氧化和还原后结合胆固醇的能力.
主要成果:
- STARD3不仅结合MSRA,而且还结合了所有三个MSRB酶.
- STARD3的氨酸残留物 (Met307和Met427) 被胆固醇-6α-氧化物和胆固醇-7α-氧化物氧化.
- MSR酶减少了氧化氨酸残留物,恢复了STARD3的胆固醇结合能力.
- 这种循环氧化减氧机制可以排毒胆固醇.
结论:
- 通过可逆的甲氨酸氧化,STARD3在排毒细胞毒性胆固醇氧化物中发挥着直接作用.
- 与MSRs的相互作用促进了这种解毒过程,保护细胞组件.
- 这代表了一种用于管理胆固醇运输过程中氧化损伤的新型催化机制.
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