[en] The impact of the ribosome exit tunnel electrostatics on the protein elongation rate or on the
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 minus 40% to plus 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 derived, 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, the shape and the size of the tunnel. The model
consistently connects experimental observations coming from different fields in molecular biology,
X-ray crystallography, physical chemistry, biomechanics, synthetic and multi-omics biology. Our
model should be a valuable tool to gain insight into protein synthesis dynamics, translational control
and into the role of the ribosome's mechanochemistry in the co-translational protein folding.
Research Center/Unit :
Biomech Research Unit
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Joiret, Marc ; Université de Liège - ULiège > GIGA In silico medecine - Biomechanics Research Unit
Rapino, Francesca ; Université de Liège - ULiège > GIGA Stem Cells - Cancer Signaling
Close, Pierre ; Université de Liège - ULiège > GIGA Stem Cells - Cancer Signaling
Geris, Liesbet ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique
Language :
English
Title :
Ribosome exit tunnel electrostatics
Publication date :
09 September 2021
Number of pages :
A5
Event name :
EMBO - Workshop - Protein synthesis and translational control
Event organizer :
European Molecular Biology Organization
Event place :
Heidelberg, Germany
Event date :
from 07-09-2021 to 10-09-2021
Audience :
International
Name of the research project :
Joint t against osteoarthritis; ERC grant agreement n°772418 (INSITE)
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique WELBIO - Walloon Excellence in Life Sciences and Biotechnology