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一个ATP13A1辅助的拓生成途径,用于折叠多跨度膜蛋白

Jia Ji¹, Meng-Ke Cui¹, Rong Zou¹

¹Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Road, Shanghai 201210, China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100101, China.

|May 9, 2024

概括

新发现的翻译后通路有助于在蛋白质中正确插入困难的跨膜域 (pTMDs). 这种机制确保了正确的蛋白质折叠和功能,通过防止生物发生过程中的脂质暴露.

科学领域:

分子生物学分子生物学
细胞生物学细胞生物学
蛋白质折叠蛋白质的折叠

背景情况:

多跨膜蛋白通常具有不良的疏水性跨膜域 (pTMD).
新生的pTMDs在插入内质网膜时对转位构成挑战.
辨别和整合这些困难的pTMDs到成熟的蛋白质结构的机制尚未完全理解.

研究的目的:

阐明管理pTMDs的识别和整合的翻译后途径.
了解pTMDs是如何正确地折叠和嵌入多跨度膜蛋白中的困难.

主要方法:

作为一个模型系统,利用了六个跨度的蛋白质ABCG2 (腺三酸盐结合盒载体G2).
采用培养的人体细胞来研究蛋白质拓生成.
研究了P5A-ATPase ATP13A1在这个过程中的作用.
研究了ATP13A1耗尽和pTMD残留物破坏的影响.

主要成果:

证明了ABCG2的pTMD2可以通过转位孔进入ER光层,形成与误导的跨膜域 (TMDs) 的中间体.
表明P5A-ATPase ATP13A1在翻译后被招募,以促进TMD重新定位和正确折叠.
观察到ATP13A1的耗尽或破坏pTMD残留物导致暴露和误导的TMD的中介物被停止.

结论:

一个新的翻译后拓生成途径负责难以整合的pTMDs.
ATP13A1在pTMD的晚期折叠和正确埋葬中起着至关重要的作用,防止脂质暴露.
这种机制确保了含有具有挑战性的疏水区域的多跨度膜蛋白的适当结构和功能.

关键词:

这就是ABCG2ABCG2.在 ATP13A1 中,边缘性疏水的TMD是一种边缘性疏水的TMD.膜蛋白的折叠膜蛋白的折叠膜蛋白质的拓发生.多跨度膜蛋白质是多跨度膜蛋白质.缺乏疏水性的TMD.重新定位的重定位是指重定位.拓学的拓学跨膜域域是一个跨膜域.

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