Poster Session - Abstract # 20

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

Erick McCloskey¹, Scott Lovell², Maithri M. Kashipathy², Philip Gao³, Anne L. Cooper³, David K. Johnson⁴, and David J. Davido¹

¹Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA; ²Protein Structure and X-Ray Crystallography Laboratory, University of Kansas, Lawrence, KS, USA; ³Protein Production Group, University of Kansas, Lawrence, KS, USA; ⁴Chemical Computational Biology Core, University of Kansas, Lawrence, KS, USA

Infected cell protein 0 (ICP0) is an immediate-early regulatory protein of herpes simplex virus 1 (HSV-1) that possesses E3 ubiquitin ligase activity.  ICP0 transactivates viral genes, in part, through its C-terminal dimer domain (residues 555-767).  Deletions in this dimer domain result in reduced viral gene expression, lytic infection, and reactivation from latency.  Since ICP0’s dimer domain is associated with its transactivation activity and efficient HSV-1 replication, we wanted to determine the structure of this specific domain.  ICP0 was purified from bacteria and analyzed by X-ray crystallography to solve its structure.  Each subunit or monomer in the ICP0 dimer is composed of nine β-sheets and two α-helices.  Interestingly, 2 adjacent β-sheets from one monomer “reach” into adjacent subunit during dimer formation, generating 2 β-barrel-like motifs.  Additionally, from the crystallographic analyses, a tetramer structure is formed from 2 β-sheets of each dimer, creating a “stacking” of the β-barrels.  Structural protein database searches indicate the fold/structure adopted by the ICP0 dimer is novel, and its dimer is held together by an extensive network of hydrogen bonds.  Computational analyses reveal that ICP0 can either form a dimer or bind to SUMO1 via its C-terminal SUMO-interacting motifs but not both.  Understanding the structure of the dimer domain will provide insights into the activities of ICP0.