CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain.
Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Gottingen, Germany.
EMBO J. 2022 Feb 15;41(4):e109175. doi: 10.15252/embj.2021109175. Epub 2022 Jan 7.
Cellular proteins begin to fold as they emerge from the ribosome. The folding landscape of nascent chains is not only shaped by their amino acid sequence but also by the interactions with the ribosome. Here, we combine biophysical methods with cryo-EM structure determination to show that folding of a β-barrel protein begins with formation of a dynamic α-helix inside the ribosome. As the growing peptide reaches the end of the tunnel, the N-terminal part of the nascent chain refolds to a β-hairpin structure that remains dynamic until its release from the ribosome. Contacts with the ribosome and structure of the peptidyl transferase center depend on nascent chain conformation. These results indicate that proteins may start out as α-helices inside the tunnel and switch into their native folds only as they emerge from the ribosome. Moreover, the correlation of nascent chain conformations with reorientation of key residues of the ribosomal peptidyl-transferase center suggest that protein folding could modulate ribosome activity.
细胞蛋白质在从核糖体中出来时开始折叠。新生链的折叠景观不仅由其氨基酸序列决定，还与其与核糖体的相互作用有关。在这里，我们结合生物物理方法和冷冻电镜结构测定，表明β桶蛋白的折叠始于核糖体内部形成动态的α螺旋。随着生长肽到达隧道的末端，新生链的 N 端部分重新折叠成β发夹结构，该结构保持动态，直到从核糖体中释放出来。与核糖体的接触和肽基转移酶中心的结构取决于新生链构象。这些结果表明，蛋白质可能在隧道内以α螺旋开始，并在从核糖体中出来时才切换到其天然构象。此外，新生链构象与核糖体肽基转移酶中心关键残基的重新取向的相关性表明，蛋白质折叠可能调节核糖体的活性。
