Ribosome Elongation Kinetics of Consecutively Charged Residues Are Coupled to Electrostatic Force

Sarah E. Leininger, Judith Rodriguez, Quyen V. Vu, Yang Jiang, Mai Suan Li, Carol Deutsch, Edward P. O'Brien

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The speed of protein synthesis can dramatically change when consecutively charged residues are incorporated into an elongating nascent protein by the ribosome. The molecular origins of this class of allosteric coupling remain unknown. We demonstrate, using multiscale simulations, that positively charged residues generate large forces that move the P-site amino acid away from the A-site amino acid. Negatively charged residues generate forces of similar magnitude but move the A- and P-sites closer together. These conformational changes, respectively, increase and decrease the transition state barrier height to peptide bond formation, explaining how charged residues mechanochemically alter translation speed. This mechanochemical mechanism is consistent with in vivo ribosome profiling data exhibiting proportionality between translation speed and the number of charged residues, experimental data characterizing nascent chain conformations, and a previously published cryo-EM structure of a ribosome-nascent chain complex containing consecutive lysines. These results expand the role of mechanochemistry in translation and provide a framework for interpreting experimental results on translation speed.

Original languageEnglish (US)
Pages (from-to)3223-3235
Number of pages13
JournalBiochemistry
Volume60
Issue number43
DOIs
StatePublished - Nov 2 2021

All Science Journal Classification (ASJC) codes

  • Biochemistry

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