Biology Reference
In-Depth Information
Table 4.3. Fusion Peptide Characteristics from the Fusion Protein from Different Classes
Fusion peptide
Class I
Class II
Class III
Initial situation
Buried in trimer interface
Buried in the dimer
interface
Buried in the interface
between different
trimers
Localization
N-term (HIV, HA2,
etc.) or internal (RSV,
Ebola, etc.)
Internal loop embedded
between 2 beta-
strands
2 internal loop
(segmented fusion
peptide; nonobvious
on primary sequence)
Structure
flexibility
Alpha helix
$
random
Stable random
$
coil
Alpha helix
$
random
coil/turn
and turn
coil/turn
Interaction with
membrane
Insert into one bilayer
leaflet
Stay at the membrane
surface (insert into
hydrocarbon chains
of the outer leaflet)
Stay at the membrane
surface (insert into
hydrocarbon chains
of the outer leaflet)
Maturation to
prefusion state
through
Proteolytic processing of
fusion protein
(except Ebola, Sars)
Proteolytic processing
of companion protein
No proteolytic process
Activated in the
glycoprotein
complex
2 proteins (PIV 5)
1 cleaved protein (HA)
1 uncleaved (Ebo,SARS)
2 identical or different
proteins (SFV,
TBEV)
1 uncleaved protein (G)
3 proteins (gB with
gH/gL)
Contrary to the relatively simple and canonical organization of the fusion
peptides for the influenza virus or the flavivirus E protein, the recently resolved
structures of the gB glycoprotein of the simplex herpes type 1 virus (Heldwein
et al
., 2006, 2007) of the vesicular stomatitis
virus (VSV) indicated a bipartite fusion peptide composed of two hydrophobic
loops, each loop being relatively nonpolar or very weakly hydrophobic (which
rarely leads to the identification of a fusion peptide by fusion peptide prediction
based on hydrophobic domain identification). These differences in the organiza-
tion of the fusion peptides suggest differences of action of the fusion proteins,
notably in the number required. According to experiments using neutralization
assays, it seems that one HIV envelope glycoprotein is capable of inducing
membrane fusion. However, it has been shown that the induced fusion by HA
requires a collaboration of several complexes of envelope glycoprotein (8-9
trimers). In the same way, different networks of class II fusion proteins have
been proposed, such as the hexagonal organization observed on the surface of
liposomes or an association of five trimers in a structure similar to a volcano
based on structure predictions (Stiasny and Heinz, 2006). Concerning the fusion
protein of class III, a hexagonal structure has been proposed for rabies virus
envelope glycoprotein and recently for VSV-G according to a modeling using its
structure. The requirement for multiple fusion peptides may be compared to the
., 2006) and G protein (Roche
et al
