Biomechanics Research Unit, GIGA In Silico Medicine, Liège University, CHU-B34(+5) 1 Avenue de l'Hôpital, 4000 Liège, Belgium.
UR InBios, Centre d'Ingénierie des Protéines, Bât B6a, Allée du 6 Août, 19, B-4000 Liège, Belgium.
Phys Rev E. 2022 Jan;105(1-1):014409. doi: 10.1103/PhysRevE.105.014409.
The impact of ribosome exit tunnel electrostatics on the protein elongation rate or on forces acting upon the nascent polypeptide chain are currently not fully elucidated. In the past, researchers have measured the electrostatic potential inside the ribosome polypeptide exit tunnel at a limited number of spatial points, at least in rabbit reticulocytes. Here we present a basic electrostatic model of the exit tunnel of the ribosome, providing a quantitative physical description of the tunnel interaction with the nascent proteins at all centro-axial points inside the tunnel. We show that a strong electrostatic screening is due to water molecules (not mobile ions) attracted to the ribosomal nucleic acid phosphate moieties buried in the immediate vicinity of the tunnel wall. We also show how the tunnel wall components and local ribosomal protein protrusions impact on the electrostatic potential profile and impede charged amino acid residues from progressing through the tunnel, affecting the elongation rate in a range of -40% to +85% when compared to the average elongation rate. The time spent by the ribosome to decode the genetic encrypted message is constrained accordingly. We quantitatively derive, at single-residue resolution, the axial forces acting on the nascent peptide from its particular sequence embedded in the tunnel. The model sheds light on how the experimental data point measurements of the potential are linked to the local structural chemistry of the inner wall, shape, and size of the tunnel. The model consistently connects experimental observations coming from different fields in molecular biology, x-ray crystallography, physical chemistry, biomechanics, and synthetic and multiomics biology. Our model should be a valuable tool to gain insight into protein synthesis dynamics, translational control, and the role of the ribosome's mechanochemistry in the cotranslational protein folding.
核糖体出口隧道静电学对蛋白质延伸速度或新生多肽链上的力的影响目前尚未完全阐明。过去，研究人员在有限的空间点测量了核糖体多肽出口隧道内的静电势，至少在兔网织红细胞中是如此。在这里，我们提出了核糖体出口隧道的基本静电模型，为隧道与隧道内所有中心轴点的新生蛋白质的相互作用提供了定量的物理描述。我们表明，强烈的静电屏蔽是由于水分子（而不是可移动离子）被吸引到核糖体核酸磷酸盐部分，这些部分埋藏在隧道壁的附近。我们还展示了隧道壁成分和局部核糖体蛋白突出物如何影响静电势分布，并阻碍带电荷的氨基酸残基通过隧道前进，与平均延伸速度相比，延伸速度降低了 -40%至 +85%。核糖体解码遗传加密信息的时间也相应受到限制。我们以单残基分辨率定量推导了作用在隧道中嵌入的新生肽上的轴向力，该力来自其特定序列。该模型阐明了实验数据点如何与内壁的局部结构化学、隧道的形状和大小相关联。该模型一致地将来自分子生物学、X 射线晶体学、物理化学、生物力学以及合成和多组学生物学等不同领域的实验观察结果联系起来。我们的模型应该是深入了解蛋白质合成动力学、翻译控制以及核糖体机械化学在共翻译蛋白质折叠中的作用的有价值的工具。
