美国芝加哥大学Robert J. Keenan团队近期取得重要工作进展，他们研究发现底物驱动的多通道膜蛋白易位子的组装。这一研究成果2022年10月19日在线发表于《自然》杂志上。
研究人员定义了一个专门用于多通道膜蛋白生成的易位子的组成、功能和组装。这种 "多通道易位子 "由三个组件区分，它们在多通道蛋白质合成过程中选择性地与核糖体-Sec61复合物结合：GET-和EMC-like（GEL）、与易位子相关的蛋白质（PAT）和Sec61的背侧（BOS）复合物。对插入中间物的分析揭示了新生链的特征是如何触发多通道易位基因组装的。重组研究证明了多通道易位子组件在蛋白质拓扑结构中的作用，缺乏这些组件的细胞显示出多通道蛋白质稳定性降低。
这些结果确立了新生的多通道蛋白选择性地招募多通道易位子以促进其生物生成的机制。更广泛地说，研究人员将ER易位子定义为一个动态的组合，其亚基组成调整协同翻译以适应其不同底物的生物合成需求。
据介绍，大多数膜蛋白是在内质网（ER）结合的核糖体上合成的，核糖体停靠在易位子上，这是一个跨膜因子的异质性组合，作用于新生的链上。易位子如何协调这些因素的作用以适应其不同的底物目前还不清楚。
附：英文原文
Title: Substrate-driven assembly of a translocon for multipass membrane proteins
Author: Sundaram, Arunkumar, Yamsek, Melvin, Zhong, Frank, Hooda, Yogesh, Hegde, Ramanujan S., Keenan, Robert J.
Issue&Volume: 2022-10-19
Abstract: Most membrane proteins are synthesized on endoplasmic reticulum (ER)-bound ribosomes docked at the translocon, a heterogeneous ensemble of transmembrane factors operating on the nascent chain1,2. How the translocon coordinates the actions of these factors to accommodate its different substrates is not well understood. Here we define the composition, function and assembly of a translocon specialized for multipass membrane protein biogenesis3. This ‘multipass translocon’ is distinguished by three components that selectively bind the ribosome–Sec61 complex during multipass protein synthesis: the GET- and EMC-like (GEL), protein associated with translocon (PAT) and back of Sec61 (BOS) complexes. Analysis of insertion intermediates reveals how features of the nascent chain trigger multipass translocon assembly. Reconstitution studies demonstrate a role for multipass translocon components in protein topogenesis, and cells lacking these components show reduced multipass protein stability. These results establish the mechanism by which nascent multipass proteins selectively recruit the multipass translocon to facilitate their biogenesis. More broadly, they define the ER translocon as a dynamic assembly whose subunit composition adjusts co-translationally to accommodate the biosynthetic needs of its diverse range of substrates.
DOI: 10.1038/s41586-022-05330-8
Source: https://www.nature.com/articles/s41586-022-05330-8
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
