dc.contributor.advisor | Grubmüller, Helmut Prof. Dr. | |
dc.contributor.author | Gabrielli, Sara | |
dc.date.accessioned | 2024-12-17T10:12:49Z | |
dc.date.issued | 2024-12-17 | |
dc.identifier.uri | http://resolver.sub.uni-goettingen.de/purl?ediss-11858/15688 | |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-10909 | |
dc.format.extent | 133 | de |
dc.language.iso | eng | de |
dc.subject.ddc | 571.4 | de |
dc.title | Mechanisms of Ribosomal Translation studied by Molecular Dynamics Simulations | de |
dc.type | cumulativeThesis | de |
dc.contributor.referee | Bennati, Marina Prof. Dr. | |
dc.date.examination | 2024-06-21 | de |
dc.description.abstracteng | During 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.coReferee | Stark, Holger Prof. Dr. | |
dc.subject.eng | Elongation Factor-G | de |
dc.subject.eng | ribosome | de |
dc.subject.eng | ribosome simulation | de |
dc.subject.eng | RAPP stallers | de |
dc.subject.eng | SecM | de |
dc.subject.eng | molecular dynamics | de |
dc.subject.eng | computational biophysics | de |
dc.identifier.urn | urn:nbn:de:gbv:7-ediss-15688-3 | |
dc.date.embargoed | 2025-06-20 | |
dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
dc.subject.gokfull | Biologie (PPN619462639) | de |
dc.description.embargoed | 2025-06-20 | de |
dc.identifier.ppn | 1914849671 | |
dc.identifier.orcid | 0000-0002-3021-6094 | de |
dc.notes.confirmationsent | Confirmation sent 2024-12-17T10:15:01 | de |