PROTEIN SUBUNIT STRUCTURES IN THE HERPES-SIMPLEX VIRUS A-CAPSID DETERMINED FROM 400-KV SPOT-SCAN ELECTRON CRYOMICROSCOPY

The three-dimensional structure of the A-capsid of herpes simplex viru s type-1 has been determined to a resolution of similar to 26 Angstrom by using 400 kV spot-scan electron cryomicroscopy and computer image reconstruction techniques. The density map of the capsid has revealed several new structural details in the protein subunits of pentons, her ons, and triplexes. Our structural analysis has provided further evide nce for the assignment of the four major capsid proteins to these vari ous subunits. VP5, a 150 kDa major capsid protein that makes up both t he penton and the bulk of the hexon subunits, has three domains: an up per diamond-shaped domain, a middle stem-like domain, and a lower anch oring domain. Structural differences are noticeable between the VP5 su bunits in various quasi-equivalent environments. A horn-shaped mass de nsity present at the distal end of each hexon subunit but missing from the penton subunit has been assigned to VP26, a minor 12 kDa protein. The six types of triplexes have similar, but not identical, features that include two legs and an upper domain that has a tail, which are i nterpreted to be formed from two copies of VP23 (36 kDa) and one copy of VP19c (57 kDa), respectively. Each tripler has two arms that intera ct with the adjacent VP5 subunits, and the modes of interaction vary a mong the quasi-equivalent triplexes. The 25 Angstrom-thick floor of th e capsid is formed by the close association of the lower domains of su bunits from the herons, pentons, and triplexes. The interior of the ca psid is accessible through the trans-capsomeric channels and the holes at the base of each tripler. These openings may play a role in the tr ansport of genomic DNA and scaffolding proteins during capsid morphoge nesis.