9OPC

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

9OPC の概要

• エントリーDOI: 10.2210/pdb9opc/pdb
• EMDBエントリー: 70691
• 分子名称: Capsid portal protein (1 entity in total)
• 機能のキーワード: complex, viral protein
• 由来する生物種: Human alphaherpesvirus 1 strain KOS
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 890142.28

構造登録者

Crofut, E.H.,Kashyap, S.,Stevens, A.,Jih, J.,Liu, Y.-T.,Zhou, Z.H. (登録日: 2025-05-18, 公開日: 2025-05-28, 最終更新日: 2025-08-06)

主引用文献

Stevens, A.,Kashyap, S.,Crofut, E.,Alvarez-Cabrera, A.L.,Jih, J.,Liu, Y.-.T.,Zhou, Z.H.
Structure of a new capsid form and comparison with A-, B-, and C-capsids clarify herpesvirus assembly.
J.Virol., 99:e0050425-e0050425, 2025

PubMed Abstract: Three capsid types have been recognized from the nuclei of herpesvirus-infected cells: empty A-capsids, scaffolding-containing B-capsids, and DNA-filled C-capsids. Despite progress in determining atomic structures of these capsids and extracellular virions in recent years, debate persists concerning the origins and temporal relationships among these capsids during capsid assembly and genome packaging. Here, we have imaged over 300,000 capsids of herpes simplex virus type 1 by cryogenic electron microscopy (cryoEM) and exhaustively classified them to characterize the structural heterogeneity of the DNA-translocating portal complex and their functional states. The resultant atomic structures reveal not only the expected A-, B-, and C-capsids but also capsids with portal vertices similar to C-capsids but no resolvable genome in the capsid lumen, which we named D-capsids. The dodecameric dsDNA-translocating portal complex varies across these capsid types in their radial positions in icosahedral capsids and exhibits structural dynamics within each capsid type. In D-capsids, terminal DNA density exists in multiple conformations including one reminiscent of that in C-capsids, suggesting D-capsids are products of failed DNA retention. This interpretation is supported by varying amounts of DNA outside individual D-capsids and by the correlation of capsid counts observed of infected cell nuclei and those after purification. Additionally, an "anchoring" segment of the scaffold protein is resolved interacting with the portal baskets of A- and B-capsids but not D- and C-capsids. Taken together, our data indicate that A-capsids arise from failed DNA packaging and D-capsids from failed genome retention, clarifying the origins of empty capsids in herpesvirus assembly.IMPORTANCEAs the prototypical herpesvirus, herpes simplex virus 1 (HSV-1) exhibits a global seroprevalence of 67% and approaching 90% in some localities. Herpesvirus infections can cause devastating cancers and birth defects, with HSV-1 infections leading to cold sores among the general population worldwide and blindness in developing nations. Here, we present atomic structures of the capsids sorted out from the nuclear isolates of HSV-1 infected cells, including the previously recognized A-, B-, and C-capsids, as well as the newly identified D-capsid. The structures show the details of protein-protein and protein-DNA interactions within each capsid type and the positional and interactional variability of the viral DNA-translocating portal vertex among these capsids. Importantly, our findings suggest that A-capsids are products of failed dsDNA packaging and D-capsids of failed genome retention. Together, the high-resolution 3D structures clarify the processes of genome packaging, maintenance, and ejection during capsid assembly, which are conserved across all herpesviruses.

PubMed: 40607812
DOI: 10.1128/jvi.00504-25

実験手法

ELECTRON MICROSCOPY (4.2 Å)