Homologues of HSV-1 nuclear egress factor UL34 are potential phosphoinositide-binding proteins.
During the herpesvirus replication cycle, viral transcription, DNA replication, formation of capsids and DNA packaging occur in the nucleus. The subsequent nuclear egress of newly synthesized nucleocapsids is performed by budding of the inner leaflet of the nuclear membrane, which creates the primary envelope. Although products of two genes conserved throughout the Herpesviridae family (HSV-1 UL34 and UL31) have previously been shown to be involved in the execution of this process, the molecular basis of their activity is not clear. Here we present results of protein structure prediction for the conserved domain of UL34. The applied methodology suggests that this protein adopts a pleckstrin homology (PH) fold to perform its function. A detailed inspection of the ligand binding site strongly supports the hypothesis that UL34 orthologs can recognize phosphoinositides. Since previous works suggest that alterations of UL34 gene product result in a drastic impairment of primary envelopment of HSV-1 and trapping of capsids in the nucleus, the presented data may lead to the development of novel anti-herpetic therapeutic strategies where analogs of phosphoinositides are administered.
Wyrwicz
Lucjan S
LS
Department of Gastroenterology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland. lucjan@bioinfo.pl
Koczyk
Grzegorz
G
Rychlewski
Leszek
L
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry*; D002467:Cell Nucleus / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins / Q000737:chemistry; D010716:Phosphatidylinositols / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry*
D002352:Carrier Proteins; D019590:Nucleocapsid Proteins; D010716:Phosphatidylinositols; C403420:UL34 protein, Human herpesvirus 1; D014764:Viral Proteins