A switch from α-helical to β-strand conformation during co-translational protein folding.
A switch from α-helical to β-strand conformation during co-translational protein folding.
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DOI：
10.15252/embj.2021109175
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发表时间：
2022-02-15
期刊：
影响因子：
--
通讯作者：
Rodnina MV
中科院分区：
文献类型：
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作者：
Agirrezabala X;Samatova E;Macher M;Liutkute M;Maiti M;Gil-Carton D;Novacek J;Valle M;Rodnina MV
细胞蛋白质开始折叠，因为它们出现在核糖体。新生链的折叠景观不仅由它们的氨基酸序列形成，而且还由与核糖体的相互作用形成。在这里，我们将联合收割机生物物理方法与冷冻电镜结构测定相结合，以表明β桶蛋白的折叠始于核糖体内动态α螺旋的形成。随着生长的肽到达隧道的末端，新生链的N末端部分重新折叠成β发夹结构，该结构保持动态直到其从核糖体释放。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，只有当它们从核糖体中出现时才转换为它们的天然折叠。此外，新生链构象与核糖体肽基转移酶中心关键残基重定向的相关性表明蛋白质折叠可以调节核糖体活性。小β结构蛋白的共翻译折叠涉及在核糖体出口隧道内形成高度动态的α螺旋。
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. Co‐translational folding of a small β‐structured protein involves formation of a highly dynamic α‐helix inside the ribosome exit tunnel.