Merz Frieder, Boehringer Daniel, Schaffitzel Christiane, Preissler Steffen, Hoffmann Anja, Maier Timm, Rutkowska Anna, Lozza Jasmin, Ban Nenad, Bukau Bernd, Deuerling Elke
Zentrum für Molekulare Biologie Heidelberg, DKFZ-ZMBH Alliance, Universität Heidelberg, Heidelberg, Germany.
EMBO J. 2008 Jun 4;27(11):1622-32. doi: 10.1038/emboj.2008.89. Epub 2008 May 22.
Ribosome-associated chaperone Trigger Factor (TF) initiates folding of newly synthesized proteins in bacteria. Here, we pinpoint by site-specific crosslinking the sequence of molecular interactions of Escherichia coli TF and nascent chains during translation. Furthermore, we provide the first full-length structure of TF associated with ribosome-nascent chain complexes by using cryo-electron microscopy. In its active state, TF arches over the ribosomal exit tunnel accepting nascent chains in a protective void. The growing nascent chain initially follows a predefined path through the entire interior of TF in an unfolded conformation, and even after folding into a domain it remains accommodated inside the protective cavity of ribosome-bound TF. The adaptability to accept nascent chains of different length and folding states may explain how TF is able to assist co-translational folding of all kinds of nascent polypeptides during ongoing synthesis. Moreover, we suggest a model of how TF's chaperoning function can be coordinated with the co-translational processing and membrane targeting of nascent polypeptides by other ribosome-associated factors.
核糖体相关伴侣蛋白触发因子（TF）在细菌中启动新合成蛋白质的折叠。在这里，我们通过位点特异性交联确定了大肠杆菌TF与新生链在翻译过程中的分子相互作用序列。此外，我们利用冷冻电子显微镜首次提供了与核糖体 - 新生链复合物相关的TF全长结构。在其活性状态下，TF在核糖体出口通道上方呈拱形，在一个保护性空间中接纳新生链。正在生长的新生链最初以未折叠的构象沿着预定路径穿过TF的整个内部，即使折叠成一个结构域后，它仍被容纳在与核糖体结合的TF的保护腔内。接受不同长度和折叠状态新生链的适应性，可能解释了TF如何能够在正在进行的合成过程中协助各种新生多肽的共翻译折叠。此外，我们提出了一个模型，说明TF的伴侣功能如何与其他核糖体相关因子对新生多肽的共翻译加工和膜靶向作用相协调。
