Viruses and their crystal structure
Type of Spiritual Experience
A description of the experience
J Virol. 2015 Jun 17. pii: JVI.00441-15. [Epub ahead of print]
Structure of C-Terminal Domain of the Multifunctional ICP27 Protein from Herpes Simplex Virus-1.
Patel V1, Dahlroth SL1, Rajakannan V1, Ho HT1, Cornvik T1, Nordlund P2.
Herpes viruses are nuclear-replicating viruses that have successfully evolved to evade the immune system of humans, establishing life-long infections. ICP27 from herpes simplex virus (HSV) is a multifunctional regulatory protein that is functionally conserved in all known human herpes viruses. 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 shut-off function. It has also been implicated in several signaling pathways and 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 2.0 Å resolution. 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 out 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.
ICP27 is a key regulatory protein of the Herpes Simplex Virus and has functional homologs in all known human herpes viruses. 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.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.