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@PHDTHESIS{Bustorff:1024924,
author = {Bustorff, Nuno},
title = {{F}olding and structural studies of saccharomyces
cerevisiae {P}hosphoglycerate {K}inase},
volume = {282},
school = {RWTH Aachen University},
type = {Dissertation},
address = {Jülich},
publisher = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
reportid = {FZJ-2024-02574},
isbn = {978-3-95806-754-7},
series = {Schriften des Forschungszentrums Jülich Reihe
Schlüsseltechnologien / Key Technologies},
pages = {xxvi, 126},
year = {2024},
note = {Dissertation, RWTH Aachen University, 2024},
abstract = {Proteins are synthesized within cells by ribosomes, and
their functionality depend on the correct three-dimensional
structure obtained through the process of folding. While the
classical understanding of protein folding primarily focused
on postsynthesisfolding, recent research has shifted its
emphasis toward unraveling the intricacies of folding during
synthesis. Of particular interest in this pursuit are
multi-domain proteins, which constitute over $70\%$ of
proteins in cells. Using classical single-molecule
fluorescence resonance transfer efficiency (sm-FRET)
studies, the unfolding/refolding transitions of a two-domain
yeast phosphoglycerate kinase (yPGK) was explored as a model
for multiple domain proteins. To enhance our understanding
of a transition within a single-domain of full-length yPGK,
I assessed two FRET pair variants within the N-terminal
domain. Together with previous data we compared in total six
different variants, for which we observed three distinct
transitions in both domains: the first segment (positions
1–88 and 202–256, respectively) showed no transition
(i.e. no change in the distance), while the second segment
(positions 34–135 and 256–290, respectively) underwent a
conventional two-state transition. Intriguingly, labeling
the complete Rossmann motif (positions 1–135 and
202–290, respectively) revealed a compact intermediate
state during GuHCl-induced unfolding in transitory
conditions. The detailed understanding of N-terminal domain
transitions was essential for comparative analyses with
shorter-length proteins synthesized for co-translational
folding studies. In order to investigate the ribosomal
folding process of yPGK, I employed cryo-electron microscopy
(cryo-EM). Four distinct ribosome nascent chain complex
(RNC) structures were solved, each representing a nascent
polypeptide of a varying length. Most structures depicted
nascent chain density outside the ribosomal tunnel, and we
observed for the first time the structure of a full-length
protein nascent chain attached to the ribosome. In summary,
the presented research advances our knowledge of yPGK
folding transitions and offers novel routes for studying
co-translational folding processes within RNC complexes
using sm-FRET and cryo-EM.},
cin = {ER-C-3},
cid = {I:(DE-Juel1)ER-C-3-20170113},
pnm = {5352 - Understanding the Functionality of Soft Matter and
Biomolecular Systems (POF4-535) / 5241 - Molecular
Information Processing in Cellular Systems (POF4-524)},
pid = {G:(DE-HGF)POF4-5352 / G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)3 / PUB:(DE-HGF)11},
urn = {urn:nbn:de:0001-20240516082247276-4907644-5},
doi = {10.34734/FZJ-2024-02574},
url = {https://juser.fz-juelich.de/record/1024924},
}