Han Xiao PhD thesis - Research@StAndrews:FullText - University of ...

activity of fusion proteins (F proteins). Co-expression of HN and F protein is required for
virus-cell fusion [reviewed in (Lamb and Kolakofsky, 2001)]. Interaction between HN
and F has been reported in several studies (Deng et al., 1999; Malvoisin and Wild, 1993;
Stone-Hulslander and Morrison, 1997; Yao, Hu, and Compans, 1997).
1.2.5.6 The Fusion protein
Paramyxovirus penetration into host cells requires fusion of viral envelope with host
plasma membrane, and this process is mediated by the fusion (F) protein. F protein
expressed at the plasma membrane can also mediate fusion with neighboring cells to
form syncytia late in infection, which may facilitate virus spread. F protein is synthesized
as an class I inactive precursor protein (F 0 ), which forms a trimer, and is proteolytically
cleaved into its biologically active form F 1 and F 2 in a manner similar to other class I viral
fusion proteins, such as influenza virus hemagglutinin (HA), HIV gp160, Ebola GP, and
SARS CoV Spike protein (Colman and Lawrence, 2003; Dutch, Jardetzky, and Lamb,
2000; Earp et al., 2005; Jardetzky and Lamb, 2004). F1 contains the N-terminal fusion
peptide (FP), located at the new N-terminus after cleavage, and the hydrophobic stoptransfer
TM domain, and two heptad helical repeat regions, designated HRA and HRB.
F protein initially folds as a metastable prefusion form. The fusion activity of F protein
requires a receptor binding protein (HN, H, or G). Interaction of HN with F protein
triggers the HRA to undergo a major conformational change into the pre-hairpin
intermediate form that extends the fusion peptide outward, so that it is inserted into
membranes (Crennell et al., 2000). HRB adjacent to the TM domain then binds to HRA,
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