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 ICP0 has E3 ubiquitin ligase activity.
• ICP0's C-terminal dimer domain (residues 555-767) is vital for transactivating viral genes, viral replication, and reactivation from latency.
• Understanding the structure of this domain is key to elucidating ICP0's functions.

Purpose of the Study:

• To determine the three-dimensional structure of the C-terminal dimer domain of HSV-1 ICP0.
• To investigate the structural basis for ICP0's dimerization and its implications for function.

Main Methods:

• Purification of the ICP0 C-terminus from bacteria.
• X-ray crystallography to solve the protein structure.
• Structural database searches and computational analyses.

Main Results:

• The ICP0 dimer domain consists of nine β-strands and two α-helices per monomer.
• Dimer formation involves interdigitation of β-strands, creating novel β-barrel structures.
• Crystallographic data suggest a tetramer formation through stacked β-barrels; the fold is novel.
• ICP0 can dimerize or bind SUMO1, but not simultaneously, via its C-terminal motifs.

Conclusions:

• The determined structure of the ICP0 dimer domain is unique.
• The structural insights provide a foundation for understanding ICP0's regulatory activities.
• This knowledge will contribute to a deeper understanding of the HSV-1 life cycle.