Dynamics of peptide chains during co-translational translocation, membrane integration & domain folding
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
The biosynthesis of proteins occurs at the ribosomes, where amino acids are linked together into linear chains. Nascent protein chains may undergo several different processes during their synthesis. Some proteins begin to fold, while others interact with chaperones, targeting factors or processing enzymes. Nascent membrane proteins are targeted to the cell membrane for integration, which involves the translocation of periplasmic domains and the insertion of membrane-embedded parts.
The aim of this thesis was to gain insights about the dynamics of nascent peptide chains undergoing folding, membrane translocation and integration. To this end, we explored the use of arrest peptides (APs) as force sensors. APs stall ribosomes when translated unless there is tension in the nascent peptide chain: the higher the tension, the more full-length protein can be detected. By using APs, we could show that a transmembrane helix is strongly ‘pulled’ twice on its way into the membrane and that strong electric forces act on negatively charged peptide segments translocating through the membrane. Furthermore, we discovered that APs could be used to detect protein folding and made the surprising discovery that a small protein domain folded well inside the ribosomal tunnel. Finally, we explored the arrest-stability of a large set of AP variants and found two extremely stable APs.
Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University , 2015. , 50 p.
ribosome, membrane integration, translocation, folding, arrest peptide, SecM
Biochemistry and Molecular Biology Cell Biology Biophysics
Research subject Biochemistry
IdentifiersURN: urn:nbn:se:su:diva-121764ISBN: 978-91-7649-285-7OAI: oai:DiVA.org:su-121764DiVA: diva2:861215
2015-12-04, Magnéli Hall, Arrhenius Laboratory, Svante arrhenius väg 16 B, Stockholm, 10:00 (English)
Wilson, Daniel N., Dr
von Heijne, Gunnar, Professor
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