Dynamics of peptide chains during co-translational translocation, membrane integration & domain folding

Hedman, Rickard,1983-Stockholms universitet,Institutionen för biokemi och biofysik (author)

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.

von Heijne, Gunnar,ProfessorStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab) (thesis advisor)
Wilson, Daniel N.,DrGene Center Munich, Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany (opponent)
Stockholms universitetInstitutionen för biokemi och biofysik (creator_code:org_t)

By the author/editor: Hedman, Rickard, ...; von Heijne, Gunn ...; Wilson, Daniel N ...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biophysics

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