6OD7

Herpes simplex virus type 1 (HSV-1) pUL6 portal protein, dodecameric complex

Summary for 6OD7

• Entry DOI: 10.2210/pdb6od7/pdb
• EMDB information: 9862
• Descriptor: Portal protein (1 entity in total)
• Functional Keywords: dna-translocation, portal, dna-packaging, dodecamer, viral protein
• Biological source: Human herpesvirus 1 strain KOS (HHV-1)
• Total number of polymer chains: 12
• Total formula weight: 889950.28

Authors

Liu, Y.T.,Jih, J.,Dai, X.H.,Bi, G.Q.,Zhou, Z.H. (deposition date: 2019-03-26, release date: 2019-06-19, Last modification date: 2024-03-13)

Primary citation

Liu, Y.T.,Jih, J.,Dai, X.,Bi, G.Q.,Zhou, Z.H.
Cryo-EM structures of herpes simplex virus type 1 portal vertex and packaged genome.
Nature, 570:257-261, 2019

PubMed Abstract: Herpesviruses are enveloped viruses that are prevalent in the human population and are responsible for diverse pathologies, including cold sores, birth defects and cancers. They are characterized by a highly pressurized pseudo-icosahedral capsid-with triangulation number (T) equal to 16-encapsidating a tightly packed double-stranded DNA (dsDNA) genome. A key process in the herpesvirus life cycle involves the recruitment of an ATP-driven terminase to a unique portal vertex to recognize, package and cleave concatemeric dsDNA, ultimately giving rise to a pressurized, genome-containing virion. Although this process has been studied in dsDNA phages-with which herpesviruses bear some similarities-a lack of high-resolution in situ structures of genome-packaging machinery has prevented the elucidation of how these multi-step reactions, which require close coordination among multiple actors, occur in an integrated environment. To better define the structural basis of genome packaging and organization in herpes simplex virus type 1 (HSV-1), we developed sequential localized classification and symmetry relaxation methods to process cryo-electron microscopy (cryo-EM) images of HSV-1 virions, which enabled us to decouple and reconstruct hetero-symmetric and asymmetric elements within the pseudo-icosahedral capsid. Here we present in situ structures of the unique portal vertex, genomic termini and ordered dsDNA coils in the capsid spooled around a disordered dsDNA core. We identify tentacle-like helices and a globular complex capping the portal vertex that is not observed in phages, indicative of herpesvirus-specific adaptations in the DNA-packaging process. Finally, our atomic models of portal vertex elements reveal how the fivefold-related capsid accommodates symmetry mismatch imparted by the dodecameric portal-a longstanding mystery in icosahedral viruses-and inform possible DNA-sequence recognition and headful-sensing pathways involved in genome packaging. This work showcases how to resolve symmetry-mismatched elements in a large eukaryotic virus and provides insights into the mechanisms of herpesvirus genome packaging.

PubMed: 31142842
DOI: 10.1038/s41586-019-1248-6

Experimental method

ELECTRON MICROSCOPY (5.6 Å)