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results. Perhaps herpesviruses have achieved this evolutionary flexibility
by varying the tegument protein composition and layering another,
outer layer of tegument onto the inner layer associated with the capsid.
Structure of the Portal Complexes in
Herpesvirus Capsids
Genetic and biochemical studies have suggested the existence of a bac-
teriophage-like, DNA-packaging/ejection portal complex in hepes-
viruses, presumably located at one of the 12 vertices of each capsid of
herpesviruses. 66,67 These studies suggested that the HSV-1 portal exists
at a single vertex of the capsid, 66 a finding that is analogous to the
portal complex within DNA bacteriophages. Using cryoEM single-
particle reconstruction, Trus and colleagues demonstrated that an iso-
lated portal-like structure can self-assemble in vitro from purified UL6
protein of HSV-1. 67 However, attempts to visualize the putative herpes-
virus portal complex in its native herpesvirus capsid environment by
conventional single-particle cryoEM reconstruction approaches have
all failed due to difficulties in identifying the unique vertex based on
noisy cryoEM images by computational means.
Recently, three papers presented direct structural evidence for the
existence of a portal complex in both HSV-1 68,69 and KSHV 70 capsids
using the above discussed technique of cryoET (Fig. 5). Unfortunately,
due to the inherent resolution limit and high noise level of current
cryoET technology, the precise placement and orientation of the por-
tal complex with respect to the capsid shell remains controversial and
requires further study at an improved resolution. The internal place-
ment of an “umbilicated” portal complex, similar to bacteriophage
connectors, is supported by evidence from studies conducted by both
Deng et al . 70 and Chang et al ., 69 which were based on structures of
intact native KSHV capsids and chemically treated, penton-less HSV-1
capsids, respectively. In the latter case, high molar guanidine hydrochlo-
ride treatment was used to generate the penton-less HSV-1 capsids.
Chang et al . demonstrated that the harsh chemical treatment did not
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