Biology Reference
In-Depth Information
Third, the final steps require further refolding of the juxtamembrane
and transmembrane regions to obtain a stable postfusion structure with the
fusion peptides and the transmembrane domains at the same extremity of a
stable stem of a protein complex anchored in the target membrane. This struc-
ture brings the two membranes proximal and provides free energy to overcome
the barrier of membrane merging (Melikyan, 2008). Membrane fusion occurs,
which leads to pore formation and release of the viral genome into the
cytoplasm.
The refolding of class II fusion proteins generates trimers from mono-
meric intermediate. The existence of monomeric intermediates for class I and III
is not well known. However, if the steps that led to exposition of the fusion
peptide and its interaction with the membrane targets maintain a three-order
symmetry, the refolding of the C-terminal region requires the destruction of the
trimer at least to the juxtamembrane region. Moreover, from the differences
observed between the amino acids involved in the interface of the reconstituted
resolved trimers in their pre- and postfusion conformations, it is probable that
the conformational changes are going through a monomeric intermediate for the
class III G envelope glycoprotein of VSV and the class I F protein of paramyxo-
virus. On the contrary, the interface of the class I HA2 subunit of the HA
envelope glycoprotein trimer is very similar between the pre- and postfusion
conformation, shedding doubt on the existence of monomeric intermediates.
In contrast, when fusion is initiated at low pH, the dimers of the class II fusion
proteins are broken, freeing monomers that reassociate in trimers.
Finally, precise structural information of the native metastable confor-
mation (prefusion) and the final stable conformation (postfusion) is available
only for a limited number of viruses (for envelope glycoprotein of influenza virus,
SFV, TBEV, VSV, and the parainfluenza 5 F protein). The structural conversion
of the native metastable conformation in a final stable conformation is not
precisely known and is highly speculative for most viruses, and the envelope
glycoprotein domains implied in these molecular rearrangements are little-
referenced. Clearly, more studies are necessary to identify the intermediaries of
envelope glycoprotein conformations. These intermediates would identify the
domains that interact during the conformational changes which will highlight
ways to generate inhibitory peptides.
F. Domain organizations/fusion domains
1. Acquisition of fusion competence: Priming by cleavage
During virus production, the host cell is basically preserved, since the expression
of fusogenic competent glycoproteins is highly controlled for most viruses.
However, for some viruses, the EnvGP induce a cytopathic effect that leads to
