We have resolved the maturation of the HN protein into distinct steps using conformationally sensitive monoclonal antibodies, peptide antibodies, and HN protein mutants missing individual cysteine residues. Within the context of this pathway, we are exploring intramolecular and intermolecular disulfide bond formation, glycosylation site usage, role of carbohydrate side chains in the maturation of the protein, oligomer formation, and the role of host proteins in glycoprotein maturation. We are also beginning to explore steps in fusion protein maturation. Membrane fusion is a fundamental biological process and is involved in such diverse cellular activities as exocytosis, intracellular transport of protein from the RER to the Golgi, endocytosis, and synaptic vesicle release from nerve endings.
Membrane fusion is also central to enveloped virus infection of cells.
The paramyxovirus F protein mediates paramyxovirus membrane fusion. We are currently defining the molecular mechanisms involved in this fusion event by using mutants blocked at different stages in the fusion process. We have also shown that the HN protein is required to promote the fusion directed by the fusion protein and we are currently defining the molecular mechanism involved in this promotion.