A Hyperthermophilic Phage Decoration Protein Suggests Common Evolutionary Origin with Herpesvirus Triplex Proteins and an Anti-CRISPR Protein

Virus capsids are protein shells that protect the viral genome from environmental assaults, while maintaining the high internal pressure of the tightly packaged genome. To elucidate how capsids maintain stability under harsh conditions, we investigated the capsid components of the hyperthermophilic phage P74-26. We determined the structure of capsid protein gp87 and show that it has the same fold as decoration proteins in many other phages, despite lacking significant sequence homology. We also find that gp87 is significantly more stable than mesophilic homologs. Our analysis of the gp87 structure reveals that the core “β tulip” domain is conserved in trimeric capsid components across numerous double-stranded DNA viruses, including Herpesviruses. Moreover, this β barrel domain is found in anti-CRISPR protein AcrIIC1, suggesting a mechanism for the evolution of this Cas9 inhibitor. Our work illustrates the principles for increased stability of gp87, and extends the evolutionary reach of the β tulip domain. [Display omitted] •Structure of phage P74-26 decoration protein reveals “β tulip” domain•β Tulip domains are structurally conserved in viral proteins of various functions•Herpesvirus triplex proteins are evolutionarily related to phage decoration proteins•β Tulip is conserved in anti-CRISPR AcrIIC1, a broad-spectrum Cas9 inhibitor Structural characterization of the capsid decoration protein from a hyperthermophilic bacteriophage reveals a core β barrel domain that is conserved in trimeric proteins from numerous phages. This “β tulip” domain is also found in Herpesvirus capsid proteins as well as an anti-CRISPR protein, suggesting these proteins share a common evolutionary ancestor.