Biology Reference
In-Depth Information
It has not been possible to discern the location of KSHV SCP,
pORF65, from the cryoEM structure,
78
although preliminary
immunoEM experiments have confirmed that pORF65 is indeed
bound to the capsid.
79
Instead, Lo
et al
. labeled KSHV capsids with
anti-pORF65 antibodies and found that pORF65 binds only to the
upper domains of the hexons and not those of the pentons,
93
similar
to its counterpart in HSV-1.
Biochemical and immunoprecipitation studies by Lai and Britt
have confirmed that the 8 kDa SCP of HCMV also interacts specifi-
cally with the MCP.
91
Based on architectural similarities, it was pro-
posed that the HCMV SCP, like the SCPs of HSV-1 and KSHV,
90,92,93
binds only to MCP hexon subunits.
60,75
However, these suggestions
could not be verified by structural studies because of the low resolu-
tions of the HCMV capsid maps (~35 Å). Again, Yu
et al
. used anti-
SCP antibodies to confirm that the SCP does indeed bind only to the
hexons of HCMV.
94
Given the very different sizes and amino acid sequences of the SCPs,
it is not surprising that they should have different structural features.
HSV-1 VP26 is a two-domain protein that forms interconnected, hexa-
meric rings crowning the hexon.
90
The HCMV SCP attaches more
toward the tips of the hexon subunits, giving them an elongated appear-
ance.
75
The KSHV pORF65 appears to bind to the center of the hexon
subunit upper domain, but it does not form the horn-shaped densities
formed by VP26 on the HSV-1 hexons. These structural differences,
along with the different roles of the SCPs in infection, illustrate how evo-
lution can cause proteins to diverge in size, structure, and function even
as their interactions and location in virus architecture are preserved.
Conclusion
Three-dimensional structural studies of human herpesviruses by cryo-
electron microscopy and tomography have revealed both general
similarities in their capsid assembly and structures, as well as differences
in their tegument organization. These structural data have contributed
to the understanding of their shared and unique characteristics with
