León-González José Alberto, Flatet Perline, Juárez-Ramírez María Soledad, Farías-Rico José Arcadio
Synthetic Biology Program, Center for Genome Sciences, National Autonomous University of Mexico, Cuernavaca, Mexico.
Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Front Mol Biosci. 2022 May 30;9:851038. doi: 10.3389/fmolb.2022.851038. eCollection 2022.
Life on earth is the result of the work of proteins, the cellular nanomachines that fold into elaborated 3D structures to perform their functions. The ribosome synthesizes all the proteins of the biosphere, and many of them begin to fold during translation in a process known as cotranslational folding. In this work we discuss current advances of this field and provide computational and experimental data that highlight the role of ribosome in the evolution of protein structures. First, we used the sequence of the Ankyrin domain from the Notch receptor to launch a deep sequence-based search. With this strategy, we found a conserved 33-residue motif shared by different protein folds. Then, to see how the vectorial addition of the motif would generate a full structure we measured the folding on the ribosome of the Ankyrin repeat protein. Not only the on-ribosome folding data is in full agreement with classical biophysical measurements but also it provides experimental evidence on how folded proteins could have evolved by duplication and fusion of smaller fragments in the RNA world. Overall, we discuss how the ribosomal exit tunnel could be conceptualized as an active site that is under evolutionary pressure to influence protein folding.
地球上的生命是蛋白质作用的结果，蛋白质是细胞中的纳米机器，它们折叠成复杂的三维结构以履行其功能。核糖体合成生物圈中的所有蛋白质，其中许多蛋白质在翻译过程中就开始折叠，这一过程称为共翻译折叠。在这项工作中，我们讨论了该领域的当前进展，并提供了计算和实验数据，突出了核糖体在蛋白质结构进化中的作用。首先，我们利用Notch受体中锚蛋白结构域的序列进行了基于序列的深度搜索。通过这种策略，我们发现了不同蛋白质折叠所共有的一个保守的33个残基的基序。然后，为了观察该基序的矢量添加如何产生完整结构，我们测量了锚蛋白重复蛋白在核糖体上的折叠情况。核糖体上的折叠数据不仅与经典生物物理测量结果完全一致，而且还提供了实验证据，证明折叠蛋白可能是如何通过RNA世界中较小片段的复制和融合而进化的。总体而言，我们讨论了核糖体出口通道如何被概念化为一个处于进化压力下、影响蛋白质折叠的活性位点。
