Oxidative folding of influenza virus hemagglutinin subtypes

In this thesis project, we studied the folding process of the influenza virus hemagglutinin (HA). This transmembrane glycoprotein family is located on the surface of viral particles and executes essential functions for the infectivity of influenza viruses. Like other transmembrane glycoproteins, biosynthesis of HA takes place in the endoplasmic reticulum (ER) of infected cells, where HA first folds and then assembles into a trimer. We aimed to understand the molecular details of the folding process of HA, and studied the interplay of disulfide-bond formation and folding to expand the current knowledge on oxidative protein folding in general and on subtypes of influenza HA in particular. HA folding was known to proceed through stable intermediates to the final and native conformation. We clarified which disulfide bonds are involved in the formation of folding intermediates and established the distinct order of these transitions. This process was conserved amongst the five HA family members we examined.