Electrostatic effect of the ribosomal surface on nascent polypeptide dynamics

Anders M. Knight, Peter H. Culviner, Neşe Kurt-Yilmaz, Taisong Zou, Sefika Ozkan, Silvia Cavagnero

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The crucial molecular events accompanying protein folding in the cell are still largely unexplored. As nascent polypeptides emerge from the ribosomal exit tunnel, they come in close proximity with the highly negatively charged ribosomal surface. How is the nascent polypeptide influenced by the ribosomal surface? We address this question via the intrinsically disordered protein PIR and a number of its variably charged mutants. Two different populations are identified: one is highly spatially biased, and the other is highly dynamic. The more negatively charged nascent polypeptides emerging from the ribosome are richer in the extremely dynamic population. Hence, nascent proteins with a net negative charge are less likely to interact with the ribosome. Surprisingly, the amplitude of the local motions of the highly dynamic population is much wider than that of disordered polypeptides under physiological conditions, implying that proximity to the ribosomal surface enhances the molecular flexibility of a subpopulation of the nascent protein, much like a denaturing agent would. This effect could be important for a proper structural channeling of the nascent protein and the prevention of cotranslational kinetic trapping. Interestingly, a significant population of the highly spatially biased nascent chain, probably interacting extensively with the ribosome, is present even for very negatively charged nascent proteins. This "sticking" effect likely serves to protect nascent proteins (e.g., from cotranslational aggregation). In all, our results highlight the influence of the ribosome in nascent protein dynamics and show that the ribosome's function in protein biogenesis extends well beyond catalysis of peptide bond formation.

Original languageEnglish (US)
Pages (from-to)1195-1204
Number of pages10
JournalACS Chemical Biology
Volume8
Issue number6
DOIs
StatePublished - Jun 21 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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    Knight, A. M., Culviner, P. H., Kurt-Yilmaz, N., Zou, T., Ozkan, S., & Cavagnero, S. (2013). Electrostatic effect of the ribosomal surface on nascent polypeptide dynamics. ACS Chemical Biology, 8(6), 1195-1204. https://doi.org/10.1021/cb400030n