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or the EnvGP may reflect the adaptation of the virus to optimize the membrane
merging independently of the superficial tension. Cells are not completely round,
and superficial tension depends on the localization where the virus binds.
Moreover, the plasma membrane has different lipid compositions and interacts
with the cytoskeleton which will attenuate or increase the superficial tension at
certain localizations.
D. Structural classification: Class I, class II, and class III fusion proteins
Glycoproteins from enveloped viruses have evolved to combine two main fea-
tures. First, they have the capacity to bind with a specific cellular receptor and
second, they include a fusion domain (peptide fusion and transmembrane do-
main) that can be activated to mediate the merging (fusion) of viral and cellular
membranes.
Three different classes of viral fusion proteins have been identified to
date based on key structural features at pre- and postfusion stages. Many studies
have demonstrated that the structural transition from a pre- to a postfusion
conformation leads to a stable hairpin conformation. This includes class I fusion
proteins, characterized by trimers of hairpins containing a central alpha-helical
coiled-coil structure, and class II fusion proteins, characterized by trimers of
hairpins composed of beta structures. A third class of fusion proteins has been
described recently, that also forms trimers of hairpins by combining the two
structural elements alpha-helix and beta-sheet structures (Roche
et al.
, 2006,
2007).
The synthesis and the conformation of these classes I, II, or III fusion
proteins are different. Class I viral fusion proteins of diverse virus families,
including Retroviridae, Filoviridae, Orthomyxoviridae, Paramyxoviridae, and
Coronaviridae, differ greatly in size and amino acid sequence, but their mem-
brane-anchored domains share common structural features that are essential for
membrane fusion, including two heptad repeats (called HR-1 and HR-2), pre-
ceded by a hydrophobic fusion peptide. Class I membrane-fusion reaction is
mediated by the refolding of the fusion protein to a highly stable rod-like
structure with a central trimeric
-helical coiled coil. Such coiled-coil structures
are emblematic of class I proteins, and physical demonstration or computer
prediction of such a structure is frequently used to help define a fusion protein
as belonging to class I. The envelope glycoprotein of a retrovirus is generated by
the cleavage of its precursor in one SU and one transmembrane subunit contain-
ing an anchoring sequence to the membrane (Hunter, 1997). This maturation,
essential to the process of fusion, frees a hydrophobic sequence to the N terminal
extremity of the TM, named fusion peptide, as it is supposed to insert into the
target membrane and initiates the fusion. Initially, the fusion peptide is masked
inside the trimer of EnvGP, a form competent for the fusion (Fig. 4.2A).
