CryoEM and mutagenesis reveal that the smallest capsid protein cements and stabilizes Kaposi's sarcoma-associated herpesvirus capsid

• DOI: 10.1073/pnas.1420317112
• Publication Date: 2015-02-03T04:18:45Z
• Authors: Xinghong Dai; Danyang Gong; Yuchen Xiao; Ting-Ting Wu; Ren Sun; Z. Hong Zhou
• Keywords: 0301 basic medicine; capsid stabilization; Protein Conformation; smallest capsid protein; Molecular Sequence Data; 610; Sequence Homology; Cell Line; 03 medical and health sciences; Capsid; 616; cementing protein; Humans; Amino Acid Sequence; Herpesvirus 8; capsid assembly; Cancer; DNA Primers; Base Sequence; Sequence Homology, Amino Acid; Cryoelectron Microscopy; Biological Sciences; Kaposi's sarcoma-associated herpesvirus; 3. Good health; Amino Acid; Emerging Infectious Diseases; Infectious Diseases; Mutagenesis; Herpesvirus 8, Human; Biochemistry and Cell Biology; Generic health relevance; Infection; Human

Significance Kaposi's sarcoma-associated herpesvirus (KSHV) and EBV are cancer-causing human herpesviruses. Their smallest capsid proteins (SCPs) were shown to be required for capsid assembly and are potential drug targets for curbing viral infections, but how they work is unclear. By cryoEM and genetic engineering, we determine the structures of KSHV capsids bearing full-length or truncated SCPs and localize regions of SCP that are important for capsid assembly. We show that a long kinked helix of SCP cross-links neighboring subunits of the major capsid protein of hexons to stabilize the capsid. Our results explain how SCP, acting like a cementing protein found in bacterial viruses, facilitates tumor herpesvirus capsid assembly and viral maturation.