ZHMB-Kolloquium: ER protein translocation in virology

ER protein translocation in virology

In eukaryotes, about 30% of the proteome is translocated across the endoplasmic reticulum (ER) membrane. It is the first step in the biosynthesis of polypeptide precursors for many soluble proteins (with amino-terminal signal peptides) and integral membrane proteins (possessing hydrophobic transmembrane helices) in secretory pathway compartments, the plasma membrane, and in the extracellular environment. Translocation and membrane insertion of nascent peptide chains are mostly mediated by the heterotrimeric Sec61 complex formed by Sec61α, Sec61β, and Sec61γ subunits that span the eukaryotic ER membrane. There is significant interest in identifying small-molecule inhibitors of Sec61 that may either only block protein import selectively, or that may be used at sub-toxic concentrations. Such Sec61 inhibitors are of interest as e.g. putative anticancer or immunosuppressive agents. 

Also, enveloped viruses (such as dengue virus) rely on the co-translational translocation process into the ER to get their viral envelope proteins expressed in the membrane of new virions that bud from an infected cell. In this presentation I will discuss the potential of the cyclotriazadisulfonamide (CADA) compounds as Sec61-targeted translocon inhibitors in the context of antiviral treatment. 

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