Final Report Summary - CELCELFUS (Cell-Cell fusion in fertilization and developmental biology: a structural biology approach)
The viral class II membrane fusion proteins occur in RNA viruses displaying a regular lattice of surface glycoproteins. They have the capacity of controlling membrane curvature and drive the process of budding of closed viral particles. Their organization at the surface of virus particles keeps them trapped in a metastable state. Only when they are incorporated into their host cell by endocytosis, they are triggered by the acidic environment of the endosome to undergo a fusogenic conformational transition. The end point of this transition is their trimeric post-fusion state - the same state in which we characterized HAP2 in our structural studies. Very recently, we have identified a conformation of HAP2 that is different, which likely corresponds to its pre-fusion form. Our results now open the way to understand the details of the fusogenic conformational change of HAP2, and also how HAP2 is organized at the cell surface prior to fusion. The results from the Celcelfus grant have now put us in a situation of exploring HAP2 function - inspired from the mechanism of action of their viral counterparts - that we could not have suspected five years ago, when applying for the grant.