Conserved domains and structure prediction of human cytomegalovirus UL27 protein.
BACKGROUND
The human cytomegalovirus (HCMV) nuclear UL27 protein (pUL27) could be involved at the stage of nuclear egress. Maribavir is a new anti-HCMV drug that targets nuclear egress through direct inhibition of the HCMV serine-threonine kinase, UL97 protein (pUL97). Because maribavir-resistance-related mutations are observed in both proteins, pUL27 is thought to interfere with pUL97 activity; however, its mechanism of action remains unclear.


METHODS
As there is no available crystal structure for pUL27 or any known structures of its homologous proteins, we attempted to identify pUL27 functional domains by sequence analysis, identification of conserved domains, structure prediction and matching with previously known maribavir resistance mutations.


RESULTS
The UL27 sequence analysis of 20 HCMV wild-type strains and 8 ganciclovir-resistant HCMV strains allowed us to describe four conserved domains, to localize the putative phosphorylation sites and to identify protein-protein interface domains, suggesting that pUL27 could interact with either pUL97 or itself.


CONCLUSIONS
Although the function of pUL27 is still unknown in the HCMV replication cycle, our approach identified target domains that appeared to be essential to the function of pUL27. This work provides a better understanding on the relative importance of each pUL27 mutation and could form the basis of later comparison analyses, when a three-dimensional structure of a pUL27 homologue will be available.
Hantz
Sébastien
S
Centre National de Référence des Cytomégalovirus, Université de Limoges, EA3175, INSERM, Equipe Avenir, Limoges, France.
Couvreux
Anthony
A
Champier
Gaël
G
Trapes
Laurène
L
Cotin
Sébastien
S
Denis
François
F
Bouaziz
Serge
S
Alain
Sophie
S
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D017124:Conserved Sequence / Q000235:genetics*; D003587:Cytomegalovirus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D024882:Drug Resistance, Viral / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D012263:Ribonucleosides / Q000494:pharmacology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
D000998:Antiviral Agents; D001562:Benzimidazoles; D004279:DNA, Viral; D017853:Phosphotransferases (Alcohol Group Acceptor); D012263:Ribonucleosides; C075365:ganciclovir kinase; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole