Identification of putative functional motifs in viral proteins essential for human cytomegalovirus DNA replication.
Six of the eleven genes essential for Human cytomegalovirus (HCMV) DNA synthesis have been analyzed for putative structural motifs that may have a significant functional role in DNA replication. The genes studied encode for the DNA polymerase accessory protein (UL44), single-stranded DNA binding protein (UL57), primase-helicase complex (UL70, UL102, and UL105), and the putative initiator protein (UL84). The full-length open reading frames of these genes were highly conserved between ten isolates with amino acid sequence identity of >97% for all genes. Using ScanProsite software from the Expert Protein Analysis System (ExPASy) proteomics server, we have mapped putative motifs throughout these HCMV replication genes. Interesting motifs identified include casein kinase-2 (CKII) phosphorylation sites, a microbodies signal motif in UL57, and an ATP binding site in the putative UL105 helicase. Our investigations have also elucidated motif-rich regions of the UL44 DNA polymerase accessory protein and identified cysteine motifs that have potential implications for UL57 and UL70 primase. Taken together, these findings provide insights to regions of these HCMV replication proteins that are important for post-translation modification, activation, and overall function, and this information can be utilized to target further research into these proteins and advance the development of novel antiviral agents that target these processes.
Woon
Heng-Giap
HG
Virology Division, Department of Microbiology, SEALS, POWH and UNSW Research Laboratories, Prince of Wales Hospital, Randwick, NSW, Australia.
Scott
Gillian M
GM
Yiu
King Lun
KL
Miles
David H
DH
Rawlinson
William D
WD
D020816:Amino Acid Motifs; D000818:Animals; D017124:Conserved Sequence; D003587:Cytomegalovirus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology*; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019915:DNA Primase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D004268:DNA-Binding Proteins; D014764:Viral Proteins; D019915:DNA Primase; D004265:DNA Helicases