蛋白酶组合伴侣PSMD9的相互作用网络调节蛋白质稳定性
Joel Christie1,2, C Merlyn Anthony1,2, Mahalakshmi Harish1,2
1Protein Interactome Lab for Structural and Functional Biology, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.
这项研究揭示了PSMD9蛋白通过其EXKK基因在细胞蛋白质稳定中发挥着至关重要的作用,通过缓冲内质网膜应激和影响脂质滴形成.
科学领域:
- 细胞生物学 细胞生物学
- 分子相互作用 分子相互作用
- 蛋白质稳定机制的机制
背景情况:
- 绘制细胞功能网络和蛋白质相互作用的地图是具有挑战性的.
- 26S蛋白酶体调节子单元9 (PSMD9) 是参与蛋白酶体组装的陪伴者.
- 短线性动图 (SLiM) 调解了许多蛋白质与蛋白质的相互作用.
研究的目的:
- 调查PSMD9.9的功能网络.
- 识别和描述涉及PSMD9.9的动机驱动相互作用.
- 阐明PSMD9在细胞应激反应和蛋白质稳定中的作用.
主要方法:
- 亲和净化质谱 (AP-MS) 与SLiMFinder相结合,用于识别PSMD9相互作用体.
- 基于的结合测试以验证动机相互作用.
- 在HEK293细胞中进行PSMD9淘汰和过度表达研究,以评估功能后果.
主要成果:
- 大约20%的PSMD9相互作用器含有"EXKK"短线性图案.
- ,hnRNPA2B1和PRDX6中的EXKK基因与PSMD9的卷曲-卷曲N域结合.
- 缺少PSMD9会导致细胞内膜网膜应激,增加未折叠的蛋白质反应 (UPR),并减少脂质滴/侵蚀体的形成.
- PSMD9的再表达拯救了这些细胞表型.
结论:
- PSMD9在维持细胞蛋白质稳定中发挥着重要作用.
- EXKK图案是PSMD9的相互作用和功能的关键调解者.
- PSMD9充当细胞缓冲器,调节UPR并促进侵袭性形成,以减轻蛋白质毒性.
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