Biology Reference
In-Depth Information
acid residues, resembling the cleavage site found in the MHV S pro-
tein.
6,7
However, this region is not utilized for cleavage events in the de
novo-synthesized S protein, probably due to an unsatisfactory cleavage
motif consisting of a small number of basic amino acids. Cleavage of the
S protein is not always necessary for fusion activity of the MHV strains
14
;
however, it is important for a highly virulent strain of MHV, MHV-2.
15
The N terminal region, consisting of 330 amino acid residues in the
MHVS S1 subunit, is a receptor-binding site.
16,17
Downstream is a hyper-
variable region where mutations and deletions of various numbers of
amino acids arise during repeated passages of the virus.
18
In contrast,
SARS-CoV S protein has its receptor-binding domain not at the N ter-
minal, but rather in an internal region consisting of 193 residues at posi-
tion 318 to 510 (Fig. 1).
19
This localization of the receptor-binding site
is similar to that of group 1 coronavirus S protein, e.g., that of TGEV or
human coronavirus 229E; the S proteins of these viruses have the recep-
tor-binding domain at the position of 400-550 amino acid from the ini-
tiator of the S protein.
20
Thus, the SARS-CoV S protein is more similar
to group 1 coronavirus S protein than to MHV S protein, in terms of the
cleavability and localization of the receptor-binding site. In contrast,
there is a high similarity in the S2 subunit of MHV and the correspon-
ding region in SARS-CoV S protein. They are also very similar struc-
turally and functionally to the membrane-anchored subunit of HIV and
influenza, gp41 and HA2.
21
All of these proteins contain two heptad
repeats (HR) in the upstream of the transmembrane domain.
22-24
The
HR located upstream is named HR1 and that located downstream is
called HR2. These heptad repeats play an important role in virus-cell
membrane fusion, namely, viral entry into cells. A fusion peptide, a
hydrophobic amino acid cluster of coronavirus that penetrates into cell
membrane at an initial phase of virus-cell membrane fusion, is not located
in the N terminal region but rather in the internal not-yet identified
region of the membrane-anchored subunit of MHV S2, whereas the
SARS-CoV fusion peptide is reported in close upstream of HR1.
22-24
Coronavirus Receptors
There are at least three different types of molecule reported to work
as receptors for the various coronaviruses. The receptor protein first
