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膜间伴侣复合物促进膜蛋白生物合成
2020-08-21 15:52

英国MRC的分子生物学实验室Ramanujan S. Hegde研究小组发现一种膜间内伴侣复合物可以促进膜蛋白的生成。 该项研究成果发表在2020年8月19日的《自然》上。

研究小组首先鉴定出了PAT复合体,一种广泛保守的内质网驻留膜蛋白CCDC47和Asterix的丰富专性异二聚体。PAT复合物与新生的TMD结合,该TMD在脂质双层中包含未屏蔽的亲水性侧链,并且与底物折叠同时脱离。缺乏PAT亚基的细胞会减少多种跨膜蛋白的生成。

因此PAT复合物是一个伴侣分子,起到保护TMD,最小化多跨膜蛋白的错误折叠和维护细胞内蛋白质稳态。PAT复合物是一种膜间伴侣复合物,包含内质网驻留膜蛋白CCDC47和Asterix,可与新生的跨膜结构域直接相互作用,以促进跨膜蛋白的生成。

研究人员表示,完整的膜蛋白由大约25%的全蛋白编码基因编码。在真核生物中,大多数膜蛋白在内质网(ER)处插入、修饰和折叠。在过去的几十年的研究中,人们已经确定了膜蛋白是如何靶向内质网以及单个跨膜域(tmd)是如何插入到磷脂双分子层的。相比之下,很少有人了解多跨膜蛋白与多个TMD是如何在膜内组装的。在TMD组装过程中,极性氨基酸或带电氨基酸之间的相互作用通常会稳定最终的折叠结构。 TMD与亲水氨基酸在共转移膜蛋白的生物起源中似乎能陪同在一起。然而,内质网驻留膜蛋白的伴侣分子却严重缺乏定义和理解。本研究提供了初步的解答。

附:英文原文

Title: An intramembrane chaperone complex facilitates membrane protein biogenesis

Author: Patrick J. Chitwood, Ramanujan S. Hegde

Issue&Volume: 2020-08-19

Abstract: Integral membrane proteins are encoded by approximately 25% of all protein-coding genes1. In eukaryotes, the majority of membrane proteins are inserted, modified and folded at the endoplasmic reticulum (ER)2. Research over the past several decades has determined how membrane proteins are targeted to the ER and how individual transmembrane domains (TMDs) are inserted into the lipid bilayer3. By contrast, very little is known about how multi-spanning membrane proteins with several TMDs are assembled within the membrane. During the assembly of TMDs, interactions between polar or charged amino acids typically stabilize the final folded configuration4–8. TMDs with hydrophilic amino acids are likely to be chaperoned during the co-translational biogenesis of membrane proteins; however, ER-resident intramembrane chaperones are poorly defined. Here we identify the PAT complex, an abundant obligate heterodimer of the widely conserved ER-resident membrane proteins CCDC47 and Asterix. The PAT complex engages nascent TMDs that contain unshielded hydrophilic side chains within the lipid bilayer, and it disengages concomitant with substrate folding. Cells that lack either subunit of the PAT complex show reduced biogenesis of numerous multi-spanning membrane proteins. Thus, the PAT complex is an intramembrane chaperone that protects TMDs during assembly to minimize misfolding of multi-spanning membrane proteins and maintain cellular protein homeostasis. The PAT complex, an intermembrane chaperone complex comprising the ER-resident membrane proteins CCDC47 and Asterix, directly interacts with nascent transmembrane domains to facilitate the biogenesis of multi-spanning membrane proteins.

DOI: 10.1038/s41586-020-2624-y

Source: https://www.nature.com/articles/s41586-020-2624-y

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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