Reversing the relative time courses of the peptide bond reaction with oligopeptides of different lengths and charged amino acid distributions in the ribosome exit tunnel
Biophysics; Biochemistry; Computational biology; Mechanobiochemistry; Michaelis-Menten kinetics; Ribosome; Ribosome exit tunnel; Quench flow apparatus; Electrostatics of biomolecules; RNA; charged amino acids; picoNewtons forces; Chemical reaction time courses; Transition state; Energy barrier; Activation complex; Ribozyme
Abstract :
[en] The kinetics of the protein elongation cycle by the ribosome depends on intertwined factors. One of these factors is the electrostatic interaction of the nascent protein with the ribosome exit tunnel. In this computational biology theoretical study, we focus on the rate of the peptide bond formation and its dependence on the ribosome exit tunnel electrostatic potential profile. We quantitatively predict how oligopeptides of variable lengths can affect the peptide bond formation rate. We applied the Michaelis-Menten model as previously extended to incorporate the mechano-biochemical effects of forces on the rate of reaction at the catalytic site of the ribosome. For a given pair of carboxy-terminal amino acid substrate at the P- and an aminoacyl-tRNA at the A- sites, the relative time courses of the peptide bond formation reaction can be reversed depending on the oligopeptide sequence embedded in the tunnel and their variable lengths from the P-site. The reversal is predicted to occur from a shift in positions of charged amino acids upstream in the oligopeptidyl-tRNA at the P-site. The position shift must be adjusted by clever design of the oligopeptide probes using the electrostatic potential profile along the exit tunnel axial path. These predicted quantitative results bring strong evidence of the importance and relative contribution of the electrostatic interaction of the ribosome exit tunnel with the nascent peptide chain during elongation.
Research Center/Unit :
GIGA In silico medecine-Biomechanics Research Unit - ULiège
Kerff, Frédéric ; Université de Liège - ULiège > Département des sciences de la vie > Centre d'Ingénierie des Protéines (CIP)
Rapino, Francesca ; Université de Liège - ULiège > Département de pharmacie
Close, Pierre ; Université de Liège - ULiège > Département de pharmacie
Geris, Liesbet ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique
Language :
English
Title :
Reversing the relative time courses of the peptide bond reaction with oligopeptides of different lengths and charged amino acid distributions in the ribosome exit tunnel
Publication date :
31 May 2024
Journal title :
Computational and Structural Biotechnology Journal
ERC - European Research Council F.R.S.-FNRS - Fonds de la Recherche Scientifique WELBIO - Walloon Excellence in Life Sciences and Biotechnology
Funding number :
ERC grant agreement n°1011088919
Funding text :
This work was supported by the FNRS-FWO EOS grant 𝑛𝑜30480119
(Join-t-against-Osteoarthritis), the FNRS-WELBIO-CR-2017S-02 (THERAtRAME)
in Belgium and the European Research Council under
the European Union’s HORIZON EUROPE Framework Programme
(HEU/20214-2027) /ERC grant agreement 𝑛𝑜1011088919 (INSTant-
CARMA). The authors are grateful for the valuable contributions of the
anonymous reviewers.
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