ER陪伴者使用蛋白质折叠和质量控制的糖密码
Kevin P Guay1, Haiping Ke2, Nathan P Canniff1
1Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, Amherst, MA, USA; Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA, USA.
Molecular cell
|December 5, 2023
概括
糖密码,或N-甘氨酸特征,指导蛋白质折叠和质量控制在内质网. 特定的甘氨酸模式决定了蛇的伴侣相互作用,如α-1抗素和抗素III成熟.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- N-甘氨酸作为内质网中的关键质量控制信号,用于招募蛋白质成熟的莱克伴侣.
- N-甘氨酸的空间布局和组成,称为糖密码,是选择合适的伴侣的关键决定因素.
- 蛇 (血清蛋白酶抑制剂) 以其非序列折叠途径而闻名,导致转移稳定的活性构造.
研究的目的:
- 调查N-glycan glyco-code在人类蛇的成熟和质量控制中的作用,特别是α-1抗素 (AAT) 和抗素III (ATIII).
- 阐明甘氨酸的位置和组成如何影响蛇中的伴侣相互作用和蛋白质折叠途径.
主要方法:
- 对AAT和ATIII的N-糖甘分布和伴侣相互作用进行比较分析.
- 研究UGGT (UDP-葡萄糖糖蛋白糖转移酶) 在赛尔变种的质量控制中的作用.
- 在蛋白质折叠过程中以糖甘为媒介的陪伴者选择的特征.
主要成果:
- 具有N终端甘氨酸的AAT受益于早期的莱克陪伴者参与.
- ATIII,拥有更多的C末端甘氨酸,最初与BiP相互作用,然后通过UGGT介导的调糖.
- 对于容易发生错误折叠的蛇形病变体,UGGT活性较高,在C终端糖上发生偏好的葡萄糖化.
结论:
- 存在,位置和N-甘氨酸 (甘氨酸代码) 的组成是指导蛇的适当折叠,质量控制和贩运的重要组成部分.
- 蛇利用其特定的糖密码来有效地导航内分泌网膜质量控制系统.
- 不同的甘氨酸定位决定了鱼成熟的不同伴侣参与策略.
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