Martinez-Hackert Erik, Hendrickson Wayne A
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Cell. 2009 Sep 4;138(5):923-34. doi: 10.1016/j.cell.2009.07.044.
Trigger factor (TF) is a molecular chaperone that binds to bacterial ribosomes where it contacts emerging nascent chains, but TF is also abundant free in the cytosol where its activity is less well characterized. In vitro studies show that TF promotes protein refolding. We find here that ribosome-free TF stably associates with and rescues from misfolding a large repertoire of full-length proteins. We identify over 170 members of this cytosolic Escherichia coli TF substrate proteome, including ribosomal protein S7. We analyzed the biochemical properties of a TF:S7 complex from Thermotoga maritima and determined its crystal structure. Thereby, we obtained an atomic-level picture of a promiscuous chaperone in complex with a physiological substrate protein. The structure of the complex reveals the molecular basis of substrate recognition by TF, indicates how TF could accelerate protein folding, and suggests a role for TF in the biogenesis of protein complexes.
触发因子（TF）是一种分子伴侣，它与细菌核糖体结合，在那里接触新生的多肽链，但TF在细胞质中也大量游离，其活性在那里的特征尚不明确。体外研究表明，TF促进蛋白质重折叠。我们在此发现，无核糖体的TF能稳定地与大量全长蛋白质结合，并使其从错误折叠中恢复。我们鉴定出了这个大肠杆菌细胞质TF底物蛋白质组中的170多个成员，包括核糖体蛋白S7。我们分析了来自嗜热栖热菌的TF:S7复合物的生化特性，并确定了其晶体结构。由此，我们获得了一个与生理底物蛋白结合的通用伴侣的原子水平图像。该复合物的结构揭示了TF识别底物的分子基础，表明了TF如何加速蛋白质折叠，并暗示了TF在蛋白质复合物生物合成中的作用。
