AMOLF, Amsterdam, The Netherlands.
Department of Bionanoscience, Delft University of Technology, Van der Maasweg 9, Delft, The Netherlands.
Commun Biol. 2021 May 5;4(1):523. doi: 10.1038/s42003-021-02055-8.
Proteins commonly fold co-translationally at the ribosome, while the nascent chain emerges from the ribosomal exit tunnel. Protein domains that are sufficiently small can even fold while still located inside the tunnel. However, the effect of the tunnel on the folding dynamics of these domains is not well understood. Here, we combine optical tweezers with single-molecule FRET and molecular dynamics simulations to investigate folding of the small zinc-finger domain ADR1a inside and at the vestibule of the ribosomal tunnel. The tunnel is found to accelerate folding and stabilize the folded state, reminiscent of the effects of chaperonins. However, a simple mechanism involving stabilization by confinement does not explain the results. Instead, it appears that electrostatic interactions between the protein and ribosome contribute to the observed folding acceleration and stabilization of ADR1a.
蛋白质通常在核糖体上共翻译折叠，而新生链从核糖体出口隧道中出来。足够小的蛋白质结构域甚至可以在仍然位于隧道内时折叠。然而，隧道对这些结构域折叠动力学的影响还不是很清楚。在这里，我们将光学镊子与单分子 FRET 和分子动力学模拟相结合，研究了锌指结构域 ADR1a 在核糖体隧道内部和前庭中的折叠情况。研究发现，隧道可以加速折叠并稳定折叠状态，这让人联想到分子伴侣的作用。然而，一个简单的涉及限制稳定的机制并不能解释这些结果。相反，似乎是蛋白质和核糖体之间的静电相互作用促进了 ADR1a 的折叠加速和稳定。
