Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly
- Univ. of Alabama, Birmingham, AL (United States). Center for Biophysical Sciences and Engineering
- BioCryst Pharmaceuticals, Birmingham, AL (United States)
- Univ. of Alabama, Birmingham, AL (United States). Center for Biophysical Sciences and Engineering; Univ. of Alabama, Birmingham, AL (United States). Dept. of Medicine
Background: Uracil-DNA glycosylases (UDGs) catalyze excision of uracil from DNA. Vaccinia virus, which is the prototype of poxviruses, encodes a UDG (vvUDG) that is significantly different from the UDGs of other organisms in primary, secondary and tertiary structure and characteristic motifs. It adopted a novel catalysis-independent role in DNA replication that involves interaction with a viral protein, A20, to form the processivity factor. UDG:A20 association is essential for assembling of the processive DNA polymerase complex. The structure of the protein must have provisions for such interactions with A20. This paper provides the first glimpse into the structure of a poxvirus UDG. Results: Results of dynamic light scattering experiments and native size exclusion chromatography showed that vvUDG is a dimer in solution. The dimeric assembly is also maintained in two crystal forms. The core of vvUDG is reasonably well conserved but the structure contains one additional β-sheet at each terminus. A glycerol molecule is found in the active site of the enzyme in both crystal forms. Interaction of this glycerol molecule with the protein possibly mimics the enzyme substrate (uracil) interactions. Conclusion: The crystal structures reveal several distinctive features of vvUDG. The new structural features may have evolved for adopting novel functions in the replication machinery of poxviruses. The mode of interaction between the subunits in the dimers suggests a possible model for binding to its partner and the nature of the processivity factor in the polymerase complex.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH)
- Grant/Contract Number:
- AC02-06CH11357; U54 AI 057157; W-31-109-ENG-38
- OSTI ID:
- 1626553
- Journal Information:
- BMC Structural Biology (Online), Vol. 7, Issue 1; ISSN 1472-6807
- Publisher:
- BioMed CentralCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Similar Records
Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA glycosylase
Poxvirus uracil‐DNA glycosylase—An unusual member of the family I uracil‐DNA glycosylases