Figure 6. Model of herpesviral cleavage and packaging.

(a) Genes required for cleavage and packaging in HSV-1 and their homologs in KSHV (listed in brackets) are listed. UL15, UL28, and UL33 form the terminase complex that must dock with the portal protein (UL6), capsid, and capsid-associated proteins (including UL17). The terminase translocates the dsDNA genome into the capsid and cleaves within the terminal repeats once a full unit-length genome has been packaged. After release of the remaining genome, the UL25 portal cap binds to stabilize the packaged genome. The precise role of UL32 (KSHV ORF68) has not been determined. (b) Possible roles of ORF68 during packaging could include acting as a scaffold for the terminase to bind the nascent genome (left), acting as an adaptor terminase association with the portal (middle), or promoting formation of the initial free end on nascent genomes (right). Further potential roles include interfacing with the DNA replication machinery or late gene transcription machinery (bottom).

Figure 6—figure supplement 1. Model of DNA binding in the central channel of ORF68.

Idealized B-form DNA (PDB 1BNA) (yellow) manually docked into the central channel of ORF68. Minimal clashes with residues in the two helices facing the central channel, particularly K174, and K435, T436, D440, and R443, suggest that some conformational changes may be required to accommodate DNA spanning the central channel.