The endoplasmic reticulum (ER) is a major site for membrane protein synthesis in eukaryotes. The majority of integral membrane proteins are delivered to the ER membrane via the co-translational, signal recognition particle (SRP)-dependent route. However, tail-anchored proteins employ an alternative, post-translational route(s) that relies on distinct factors such as a cytosolic protein quality control component, SGTA. We now show that SGTA is selectively recruited to ribosomes synthesising a diverse range of membrane proteins, suggesting that its biosynthetic client base also includes precursors on the co-translational ER delivery pathway. Strikingly, SGTA is recruited to nascent membrane proteins before their transmembrane domain emerges from the ribosome. Hence, SGTA is ideally placed to capture these aggregation prone regions shortly after their synthesis. For nascent membrane proteins on the co-translational pathway, SGTA complements the role of SRP by reducing the co-translational ubiquitination of clients with multiple hydrophobic signal sequences. On this basis, we propose that SGTA acts to mask specific transmembrane domains located in complex membrane proteins until they can engage the ER translocon and become membrane inserted.

中文翻译：

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SGTA 与新生的膜蛋白前体结合。

内质网（ER）是真核生物膜蛋白合成的主要场所。大多数整合膜蛋白通过共翻译、信号识别粒子 (SRP) 依赖性途径传递到 ER 膜。然而，尾锚蛋白采用另一种翻译后途径，该途径依赖于不同的因素，如胞质蛋白质量控制成分 SGTA。我们现在表明，SGTA 被选择性地招募到合成各种膜蛋白的核糖体中，这表明其生物合成客户群还包括共翻译 ER 传递途径上的前体。引人注目的是，SGTA 在其跨膜结构域从核糖体中出现之前被招募到新生膜蛋白中。因此，SGTA 非常适合在合成后不久捕获这些易于聚集的区域。对于共翻译途径上的新生膜蛋白，SGTA 通过减少具有多个疏水信号序列的客户的共翻译泛素化来补充 SRP 的作用。在此基础上，我们建议 SGTA 起到掩盖位于复杂膜蛋白中的特定跨膜结构域的作用，直到它们可以接合 ER 易位子并插入膜。