title: Structure of the C-Terminal Domain of the Multifunctional ICP27 Protein from Herpes Simplex Virus 1.
abstract: Herpesviruses are nuclear-replicating viruses that have successfully evolved to evade the immune system of humans, establishing lifelong infections. ICP27 from herpes simplex virus is a multifunctional regulatory protein that is functionally conserved in all known human herpesviruses. It has the potential to interact with an array of cellular proteins, as well as intronless viral RNAs. ICP27 plays an essential role in viral transcription, nuclear export of intronless RNAs, translation of viral transcripts, and virion host shutoff function. It has also been implicated in several signaling pathways and the prevention of apoptosis. Although much is known about its central role in viral replication and infection, very little is known about the structure and mechanistic properties of ICP27 and its homologs. We present the first crystal structure of ICP27 C-terminal domain at a resolution of 2.0 Å. The structure reveals the C-terminal half of ICP27 to have a novel fold consisting of α-helices and long loops, along with a unique CHCC-type of zinc-binding motif. The two termini of this domain extend from the central core and hint to possibilities of making interactions. ICP27 essential domain is capable of forming self-dimers as seen in the structure, which is confirmed by analytical ultracentrifugation study. Preliminary in vitro phosphorylation assays reveal that this domain may be regulated by cellular kinases.
  
  
  OBJECTIVE
  ICP27 is a key regulatory protein of the herpes simplex virus and has functional homologs in all known human herpesviruses. Understanding the structure of this protein is a step ahead in deciphering the mechanism by which the virus thrives. In this study, we present the first structure of the C-terminal domain of ICP27 and describe its novel features. We critically analyze the structure and compare our results to the information available form earlier studies. This structure can act as a guide in future experimental designs and can add to a better understanding of mechanism of ICP27, as well as that of its homologs.
authors.affiliation: Structural Biology and Biochemistry Division, Nanyang Technological University, Singapore.
authors.forename: Vidhi
authors.identifier: http://orcid.org/0000-0002-7352-2657
authors.initials: V
authors.lastname: Patel
authors.affiliation: Structural Biology and Biochemistry Division, Nanyang Technological University, Singapore.
authors.forename: Sue-Li
authors.initials: SL
authors.lastname: Dahlroth
authors.affiliation: Structural Biology and Biochemistry Division, Nanyang Technological University, Singapore.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Rajakannan
authors.affiliation: Structural Biology and Biochemistry Division, Nanyang Technological University, Singapore.
authors.forename: Hai Ting
authors.initials: HT
authors.lastname: Ho
authors.affiliation: Structural Biology and Biochemistry Division, Nanyang Technological University, Singapore.
authors.forename: Tobias
authors.initials: T
authors.lastname: Cornvik
authors.affiliation: Structural Biology and Biochemistry Division, Nanyang Technological University, Singapore Institute of Molecular and Cell Biology, A*STAR, Singapore Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden pnordlund@ntu.edu.sg.
authors.forename: Pär
authors.initials: P
authors.lastname: Nordlund
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D018259:Herpesvirus 1, Human / Q000235:genetics*; D057927:Hydrophobic and Hydrophilic Interactions; D017874:Immediate-Early Proteins / Q000378:metabolism / Q000648:ultrastructure*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000235:genetics; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism / Q000648:ultrastructure*; D015032:Zinc / Q000378:metabolism
chemical_list: C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D012367:RNA, Viral; D014764:Viral Proteins; D015032:Zinc