Structures of the portal vertex reveal essential protein-protein interactions for Herpesvirus assembly and maturation
Nan Wang, Wenyuan Chen, Ling Zhu, Dongjie Zhu, Rui Feng, Jialing Wang, Bin Zhu, Xinzheng Zhang, Xiaoqing Chen, Xianjie Liu, Runbin Yan, Dongyao Ni, Grace Guoying Zhou, Hongrong Liu, Zihe Rao, Xiangxi Wang
Abstract
Structures of the portal vertex reveal essential protein-protein interactions for Herpesvirus assembly and maturation Dear Editor, Herpesviridae is a large family of double-stranded DNA (dsDNA) viruses that cause a variety of human diseases ranging from cold sores and chicken pox to congenital defects, blindness and cancer In the past 70 years, substantial advances in our knowledge of the molecular biology of herpesviruses have led to insights into disease pathogenesis and management. However, the mechanism for capsid assembly that requires the ordered packing of about 4,000 protein subunits into the hexons, pentons and triplexes remains elusive. It is still a puzzle how initially identical subunits adopt both hexameric and pentameric conformations in the capsid and select the correct locations needed to form closed shells of the proper size. Biochemical and genetic studies have shown that the portal is involved in initiation of capsid assembly Structural investigations of the herpesvirus portal have proven challenging due to the small size of this dodecamer, which accounts for less than 1% of the total mass of the capsid protein layer and the technical difficulties involved in resolving non-icosahedral components of such large icosahedral viruses (diameter is 1,250 ). Efforts of many investigators over two decades have made to reconstruct the cryo-electron microscopy (cryo-EM) structure of herpesvirus portal vertex and more recently near-atomic structures of two herpesvirus (herpes simplex virus type 1 (HSV-1) and Kaposi's sarcoma-associated herpesvirus (KSHV)) portal vertices were reported (McElwee et al.,