Show simple item record

Mechanisms of Ribosomal Translation studied by Molecular Dynamics Simulations

dc.contributor.advisorGrubmüller, Helmut Prof. Dr.
dc.contributor.authorGabrielli, Sara
dc.date.accessioned2024-12-17T10:12:49Z
dc.date.issued2024-12-17
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?ediss-11858/15688
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-10909
dc.format.extent133de
dc.language.isoengde
dc.subject.ddc571.4de
dc.titleMechanisms of Ribosomal Translation studied by Molecular Dynamics Simulationsde
dc.typecumulativeThesisde
dc.contributor.refereeBennati, Marina Prof. Dr.
dc.date.examination2024-06-21de
dc.description.abstractengDuring translation, the ribosome moves along the mRNA and decodes the genetic information to synthesize proteins. This process proceeds in a step-wise iterative manner during which the ribosome undergoes conformational rearrangements, together with mRNA, tRNAs and interacting protein factors. In bacteria, mechanisms have evolved that regulate gene expression by slowing down or arresting protein synthesis. I used molecular dynamics (MD) simulations to elucidate the atomistic bases of these mechanisms. In the first part of this thesis (Chapter 3), I investigated how single-point mutations in elongation factor G (EF-G), a GTPase that accelerates the translocation of the ribosome and tRNAs along the mRNA, might cause a slowdown in protein synthesis. In the second part (Chapters 4 and 5) I studied mechanisms of programmed translational stalling, i.e., the arrest of the ribosome during translation of specific peptides. In Chapter 4, I elucidated how stalling during translation of peptides containing the Arg-Ala-Pro-Pro (RAPP) motif takes place. I observed that the RAPP arrest motif rewires the hydrogen bond network required for the peptide bond formation and thereby inhibits elongation of the nascent peptide chain. In Chapter 5, I studied how the stalling in the arrest peptide SecM, which displays a similar arrest motif (RAGP) is released by a mechanical force acting on the nascent chain. By elucidating functionally relevant details of the conformational dynamics of unbound and ribosome-bound EF-G, of the peptide containing the RAPP motif, and of the SecM arrest peptide, the results of my MD simulations helped to connect structural information and biochemical data to obtain a detailed picture of atomistic mechanisms underlying ribosome regulation.de
dc.contributor.coRefereeStark, Holger Prof. Dr.
dc.subject.engElongation Factor-Gde
dc.subject.engribosomede
dc.subject.engribosome simulationde
dc.subject.engRAPP stallersde
dc.subject.engSecMde
dc.subject.engmolecular dynamicsde
dc.subject.engcomputational biophysicsde
dc.identifier.urnurn:nbn:de:gbv:7-ediss-15688-3
dc.date.embargoed2025-06-20
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de
dc.description.embargoed2025-06-20de
dc.identifier.ppn1914849671
dc.identifier.orcid0000-0002-3021-6094de
dc.notes.confirmationsentConfirmation sent 2024-12-17T10:15:01de


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record