The client spectrum of Get3, an evolutionarily conserved chaperone of membrane proteins

von Ákos Farkas
Dissertation
Datum der mündl. Prüfung:2019-11-20
Erschienen:2020-03-12
Betreuer:Prof. Dr. Blanche Schwappach-Pignataro
Gutachter:Prof. Dr. Blanche Schwappach-Pignataro
Gutachter:Dr. Alexander Stein
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-7919

 

 

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Description:Akos Farkas PhD thesis

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Englisch

Tail-anchored proteins constitute a physiologically important class of membrane proteins. Due to their topology, they are targeted post-translationally to membranes. Although Get3 is responsible for the membrane targeting of several ER-bound TA proteins, our knowledge on its in-vivo client spectrum remains limited. The oxidation-induced chaperone activity of Get3 detected in-vitro suggests that Get3 may handle further substrates besides TA proteins. My bioinformatic analysis shows that Get3-like chaperones are more widespread than previously expected and suggests that a general chaperone activity is the ancestral function of Get3. Using budding yeast as a model system, I show that although Get3 can target many TA proteins, only a fraction of them are obligate substrates of Get3. I provide evidence that an essential TA protein, Sed5, is a super-client of Get3 that interacts with it before and also after membrane targeting. I also show that Get3 can target proteins with multiple transmembrane segments located proximal to their C-terminus as part of the GET pathway. Finally, I describe membrane proteins with amphipathic helices as potential chaperone substrates of Get3. Therefore, the current study significantly expands the range of potential Get3 clients in vivo and indicates that Get3 is an important chaperone of membrane proteins both before and after membrane targeting.
Keywords: Get3; tail-anchored; chaperone
 
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