Furin-mediated protein processing in infectious diseases and cancer

Braun, Elisabeth; Sauter, Daniel

Furin cleaves the glycoproteins (GPs) of Marburg virus (MARV) and all five Ebolavirus species into a large N-terminal subunit (GP1) that mediates receptor binding and a small membrane-anchored C-terminal part (GP2) that contains the fusion , the viral envelope (Env) glycoprotein precursor (green) migrates through the ER to the Golgi complex where it is cleaved by furin (pink scissors) into the functional mature Env glycoprotein (blue). Processed Env glycoproteins are transported to the cell surface and incorporated into assembling viral particles. In contrast, dengue viruses bud into the ER lumen and incorporate the uncleaved premembrane protein (prM) (right panel). During virus particle transit through the secretory pathway, virion-associated prM proteins can be cleaved by furin (dark blue to light blue). (b) Some prM molecules escape furin-mediated cleavage in the producer cells resulting in the release of immature or partially mature dengue virus particles. In this case, processing can also occur in endosomes of new target cells, upon receptor-mediated endocytosis (left panel). During human papillomavirus (HPV) infection (right panel), attachment to heparan sulphate proteoglycans induces a conformational change that allows proteolytic processing of the minor capsid protein L2 (red) by furin, which is present at the cell surface. Furin processing induces a structural rearrangement that allows binding to a secondary receptor and subsequent receptor-mediated endocytosis.