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undergoing conformational changes at different stages of capsid assem-
bly. 22,71 The 3D folds of the protein subunits can be resolved at reso-
lutions higher than 10 Å, allowing their interactions with DNA and
other molecules to be revealed at the secondary structure level. Detailed
comparisons between members of the herpesvirus family can provide
clues as to how host specificity is determined and how viral assembly,
maturation, and host cell interactions differ between herpesviruses.
This and other structural information, such as the location of specific
epitopes of viral proteins, may be useful in designing specific antiviral
compounds.
Each herpesvirus capsid is composed of 12 pentons, 150 hexons,
and 320 connecting triplexes, which are arranged on a T
16 icosa-
hedral lattice. The major capsid protein (MCP) forms the basic struc-
tural building block of the capsid. MCP proteins are arranged in
groups of six (“hexons”) or five (“pentons”), with the pentons form-
ing the vertices of the icosahedron and the hexons filling up the
faces. The hexons have slightly different geometries depending on
their location, and are thus designated as P (penton-adjacent), E
(edge), or C (center-face). 72 Connecting the pentons and hexons are
triplexes, which act as molecular clamps and consist of one triplex
monomer protein (TRI-1) and two triplex dimer proteins (TRI-2)
each. There are six types of triplexes, designated Ta-Tf depending on
their location in the asymmetric unit. Other capsid proteins include
the small capsid protein (SCP), viral protease, and scaffold proteins
(SCAF). The capsid shell of the herpesvirus capsid has a total mass of
about 200 MDa, with 960 copies of MCP, 320 copies of TRI-1, 640
copies of TRI-2, and 900 copies of the SCP.
The capsid proteins of HSV-1, HCMV, and KSHV and their shared
sequence homologies are summarized in Table 3. Below, we provide a
detailed comparison of the capsid and capsid-associated tegument
structures across HSV-1, HCMV, and KSHV, representatives of the
alpha-, beta-, and gammaherpesvirus subfamilies, respectively.
=
HSV-1 Capsid
HSV-1 is the easiest of the human herpesviruses to culture and has
been subjected to the most extensive structural analyses among all
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