Four Levels of Hierarchical Organization, Including Noncovalent Chainmail, Brace the Mature Tumor Herpesvirus Capsid against Pressurization

• Published in: Structure (London) 2014-10, Vol.22 (10), p.1385-1398
• Main Authors: Zhou, Z. Hong, Hui, Wong Hoi, Shah, Sanket, Jih, Jonathan, O’Connor, Christine M., Sherman, Michael B., Kedes, Dean H., Schein, Stan
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Belts; Capsid - chemistry; Capsid Proteins - chemistry; Chains; Cryoelectron Microscopy; Dimerization; Epstein-Barr virus; Gammaherpesvirus; Human herpesvirus 8; Models, Molecular; Molecular Sequence Data; Monomers; Organizations; Pressurization; Pressurizing; Protein Structure, Tertiary; Rhadinovirus - chemistry; Tumors
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2014.05.019

Like many double-stranded DNA viruses, tumor gammaherpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus withstand high internal pressure. Bacteriophage HK97 uses covalent chainmail for this purpose, but how this is achieved noncovalently in the much larger gammaherpesvirus capsid is unknown. Our cryoelectron microscopy structure of a gammaherpesvirus capsid reveals a hierarchy of four levels of organization: (1) Within a hexon capsomer, each monomer of the major capsid protein (MCP), 1,378 amino acids and six domains, interacts with its neighboring MCPs at four sites. (2) Neighboring capsomers are linked in pairs by MCP dimerization domains and in groups of three by heterotrimeric triplex proteins. (3) Small (∼280 amino acids) HK97-like domains in MCP monomers alternate with triplex heterotrimers to form a belt that encircles each capsomer. (4) One hundred sixty-two belts concatenate to form noncovalent chainmail. The triplex heterotrimer orchestrates all four levels and likely drives maturation to an angular capsid that can withstand pressurization. [Display omitted] •CryoEM structure of the 1,300 Å capsid of gammaherpesvirus RRV at 7.2 Å resolution•Domain organizations and secondary structures of the four capsid proteins resolved•Noncovalent chainmail achieved via a hierarchy of four levels of organization•Triplex heterotrimers likely driving putative spherical to angular capsid maturation The cryoEM structure of a tumor herpesvirus capsid by Zhou et al. reveals an organization level’s hierarchy of protein interactions. The four levels of organization stem from the major capsid protein, culminating in formation of a noncovalent chainmail that likely helps the virus withstand high internal pressure.