DESCRIPTION (provided by applicant): Paramyxovirus infections cause disease in both humans and animals, leading to widespread morbidity, hospitalization and deaths each year. Paramyxoviruses are enveloped viruses, requiring a membrane fusion step during the entry of the virus into targeted cells. 2 proteins on the virus surface, the hemagglutinin/neuraminidase (HN) and the fusion (F) protein are responsible for receptor binding and membrane fusion in many members of the paramyxovirus family. HN binding to sialic acid receptors is thought to activate the F protein to undergo conformational changes. These conformational changes drive membrane fusion, by bringing the cellular and viral membranes together. However, the mechanisms by which receptor recognition and membrane fusion are coupled remain to be elucidated. This application is focused on investigation of the HN and F protein structures and their interactions. We propose to investigate the domain structure of the HN protein and probe its interactions with both receptor and F protein, in order to test specific hypotheses developed from previous structural and functional studies. We also propose to continue our studies of the F protein structure, its interaction with antibodies and other biologically important ligands, in order to better understand F protein conformational changes and ligand interactions that are important to virus entry. Detailed understanding of the structures and interactions of the paramyxovirus HN and F proteins may lead to novel approaches to inhibiting paramyxovirus entry into cells.
|Effective start/end date||6/1/06 → 5/31/10|
- National Institute of General Medical Sciences (2 R01 GM061050-05A2)