Peptide mimics of the vesicular stomatitis virus G-protein transmembrane segment drive membrane fusion in vitro

The efficiency of cell-cell fusion mediated by heterologously expressed ves icular stomatitis virus G-protein has previously been shown to be affected by mutating its transmembrane segment. Here, we show that a synthetic pepti de modeled after this transmembrane segment drives liposome-liposome fusion . Addition of millimolar Ca2+ concentrations strongly potentiated the effec t of the peptides suggesting that Ca2+-mediated liposome aggregation suppor ts the activity of the peptide. Peptide-driven fusion was suppressed by lys olipid, an established inhibitor of natural membrane fusion, and involved i nner and outer leaflets of the liposomal bilayer. Thus, transmembrane segme nt peptide-driven liposome fusion exhibits important hallmarks characterist ic of natural membrane fusion. Importantly, the mutations previously shown to attenuate the function of full-length G-protein in cell-cell fusion also attenuated the fusogenicity of the peptide, albeit in a less pronounced fa shion. Therefore, the function of the peptide mimic is dependent on its pri mary structure, similar to full-length G-protein. Together, our data sugges t that the G-protein transmembrane segment is an autonomous functional doma in. We propose that it acts at a late step in membrane fusion elicited by v esicular stomatitis virus.