据介绍，真核信号识别颗粒（SRP）共翻译识别新生分泌蛋白和膜蛋白的第一疏水片段，并将其传递给内质网（ER）的受体。底物如何从ER的SRP中释放出来，以随后获得易位因子，目前尚不清楚。
我们发现TMEM208可以与SRP的底物结合结构域结合，加速其结合产物的释放。没有TMEM208，缓慢的货物释放导致下游多肽在与易位因子结合之前过度合成。对易位机制的延迟访问导致插入能力的逐渐丧失，特别是对于多道膜蛋白，导致其生物发生受损。
因此，TMEM208有助于将货物从靶向转运机制迅速移交，以最大限度地减少生物发生错误并维持蛋白质稳态。
附：英文原文
Title: Identification of a factor that accelerates substrate release from the signal recognition particle
Author: Huping Wang, Ramanujan S. Hegde
Issue&Volume: 2024-11-29
Abstract: The eukaryotic signal recognition particle (SRP) cotranslationally recognizes the first hydrophobic segment of nascent secretory and membrane proteins and delivers them to a receptor at the endoplasmic reticulum (ER). How substrates are released from SRP at the ER to subsequently access translocation factors is not well understood. We found that TMEM208 can engage the substrate binding domain of SRP to accelerate release of its bound cargo. Without TMEM208, slow cargo release resulted in excessive synthesis of downstream polypeptide before engaging translocation factors. Delayed access to translocation machinery caused progressive loss of insertion competence, particularly for multipass membrane proteins, resulting in their impaired biogenesis. Thus, TMEM208 facilitates prompt cargo handover from the targeting to translocation machinery to minimize biogenesis errors and maintain protein homeostasis.
DOI: adp0787
Source: https://www.science.org/doi/10.1126/science.adp0787