HSV-1 ICP0 Dimer Domain Adopts a Novel β-barrel Fold.

Area of Science:

• Structural biology
• Virology
• Molecular biology

Background:

• Herpes simplex virus 1 (HSV-1) immediate-early protein Infected Cell Protein 0 (ICP0) regulates viral gene expression and replication.
• ICP0 possesses E3 ubiquitin ligase activity and its C-terminal dimer domain (residues 555-767) is crucial for transactivation and viral replication.
• Deletion of the dimer domain impairs viral gene expression, lytic infection, and reactivation from latency.

Approach:

• The C-terminal dimer domain of ICP0 was purified from bacterial expression.
• X-ray crystallography was employed to determine the three-dimensional structure of the ICP0 dimer domain.
• Computational analyses were performed to investigate ICP0's interaction capabilities.

Key Points:

• The ICP0 dimer consists of monomers, each with nine β-strands and two α-helices.
• Dimer formation involves interdigitation of β-strands, creating novel β-barrel structures.
• Crystallographic analysis revealed a tetramer formation through stacked β-barrels, a novel fold.
• The dimer interface is stabilized by an extensive hydrogen bond network.
• Computational studies indicate ICP0 cannot simultaneously form a dimer and bind SUMO1.

Conclusions:

• The determined structure of the ICP0 dimer domain is novel and provides a structural basis for its function.
• Understanding this structure offers critical insights into ICP0's regulatory activities.
• This knowledge will advance our comprehension of the HSV-1 life cycle and potential therapeutic targets.