Extensive subunit contacts underpin herpesvirus capsid stability and interior-to-exterior allostery

• Published in: Nature structural & molecular biology Vol. 23; no. 6; pp. 531 - 539
• Main Authors: Huet, Alexis, Makhov, Alexander M, Huffman, Jamie B, Vos, Matthijn, Homa, Fred L, Conway, James F
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-06-2016; Nature Publishing Group
• Subjects: 101/28; 631/535/1258/1259; 631/535/1267; Allosteric Regulation; Animals; Biochemistry; Biological Microscopy; Capsid - chemistry; Capsid - ultrastructure; Capsid Proteins - chemistry; Capsid Proteins - ultrastructure; Cryoelectron Microscopy; Deoxyribonucleic acid; DNA; Electron microscopy; Genetic aspects; Health aspects; Herpes Simplex - virology; Herpes simplex virus 1; Herpes viruses; Herpesvirus; Herpesvirus 1, Human - chemistry; Herpesvirus 1, Human - ultrastructure; Herpesvirus 1, Suid - chemistry; Herpesvirus 1, Suid - ultrastructure; Herpesviruses; Humans; Life Sciences; Membrane Biology; Microscopy; Models, Molecular; Molecular structure; Packaging; Properties; Protein Conformation; Protein folding; Protein Stability; Protein Structure; Protein Subunits - chemistry; Proteins; Pseudorabies - virology; Pseudorabies virus; Structure; Viral proteins; Virulence (Microbiology)
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.3212

Capsids from two herpesviruses (HSV-1 and PRV), imaged inside intact virions, are analyzed by cryo-EM. The maps allowed the construction of a complete model of subunit and domain organization, revealing extensive subunit contacts.
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.