Extensive subunit contacts underpin herpesvirus capsid stability and interior-to-exterior allostery.
The herpesvirus capsid is a complex protein assembly that includes hundreds of copies of four major subunits and lesser numbers of several minor proteins, all of which are essential for infectivity. Cryo-electron microscopy is uniquely suited for studying interactions that govern the assembly and function of such large functional complexes. Here we report two high-quality capsid structures, from human herpes simplex virus type 1 (HSV-1) and the animal pseudorabies virus (PRV), imaged inside intact virions at ~7-Å resolution. From these, we developed a complete model of subunit and domain organization and identified extensive networks of subunit contacts that underpin capsid stability and form a pathway that may signal the completion of DNA packaging from the capsid interior to outer surface, thereby initiating nuclear egress. Differences in the folding and orientation of subunit domains between herpesvirus capsids suggest that common elements have been modified for specific functions.
Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Alexis
A
Huet
Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Alexander M
AM
Makhov
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jamie B
JB
Huffman
Apps Lab, FEI Europe, Eindhoven, the Netherlands.
Matthijn
M
Vos
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Fred L
FL
Homa
Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
James F
0000-0002-6581-4748
JF
Conway
D000494:Allosteric Regulation; D000818:Animals; D002213:Capsid / Q000737:chemistry* / Q000648:ultrastructure; D036022:Capsid Proteins / Q000737:chemistry* / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000737:chemistry* / Q000648:ultrastructure; D011558:Herpesvirus 1, Suid / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D055550:Protein Stability; D021122:Protein Subunits / Q000737:chemistry; D011557:Pseudorabies / Q000821:virology
D036022:Capsid Proteins; D021122:Protein Subunits; C442523:VP5 protein, Herpes simplex virus type 1