Protein biogenesis and transport to the endoplasmic reticulum during health, aging and proteotoxic stress in Caenorhabditis elegans (A07*)

该项目研究核糖体相关新生多肽相关复合物（NAC）在蛋白质生物合成和运输中的功能。最近，我们已经发现，NAC接触新生的多肽链已经深入核糖体隧道。我们将解决这个问题，如何早期新生链隧道内的传感影响共翻译蛋白质的生物合成和运输途径。将使用秀丽隐杆线虫动物模型进行体外和体内研究。此外，我们最近发现，NAC发挥广谱分子伴侣活动，涉及多个底物结合位点。我们将对NAC的伴侣蛋白功能进行详细分析，旨在确定NAC的所有关键底物结合位点及其参与伴侣蛋白共翻译和翻译后底物的作用模式。

The project investigates the function of the ribosome-associated nascent polypeptide-associated complex (NAC) in protein biogenesis and transport. Recently, we have revealed that NAC contacts nascent polypeptide chains already deep within the ribosomal tunnel. We will address the question how the early nascent chain sensing inside the tunnel impacts co-translational protein biogenesis and transport pathways. Studies will be performed in vitro as well as in vivo using the animal model Caenorhabditis elegans. Furthermore, we recently found that NAC exerts broad-spectrum chaperone activities involving multiple substrate binding sites. We will perform a detailed analysis of the chaperone function of NAC aiming to identify all critical substrate binding sites of NAC and their modes of action involved in chaperoning co- and post-translational substrates.