Fusion Proteins and Mechanisms of Action Synaptic vesicle fusion: SNARES and C2 domains Viral Fusion: Class I and Class II Fusion Protiens

Influenza hemagglutinin

HA is class I viral fusion protein. HIV, SIV, MoMLV, HTLV, SV5, HRSV and Ebola are also class 1. All have trimeric bundle of helical hairpin with the N and C termini pointing in the same direction (fusion active form – low pH). Note: X-ray of most fusion proteins are non-complete forms, that is the transmembrane segments are removed for aid in crystallization 6 helical bundle: target of many inhibitory drugs

Class II viral membrane fusion proteins consist of three domains and form dimers on the membrane surface. pH in the endosome is the fusion “trigger”. The dimer changes to trimer. These proteins are mostly beta sheet in secondary structure. The “fusion” peptide is a short loop that protrudes from the tips of the dimerization domain Semliki virus fusion protein