Theme A Highlights
Theme A Genome targeting of archaeal viruses for new folds: Pyrobaculum spherical virus (PSV), is a dsDNA virus infecting hyperthermophilic crenarchaea of the family thermoproteales. SIRV is a rod-shaped dsDNA virus infecting the Sulfolobales. The proteins encoded by these viruses have little or no detectable homology to any proteins of known function, reflecting the extreme diversity of archaeal viruses. We have targeted all the PSV and SIRV proteins for structural studies, in the hope that the protein structures will inform our understanding of the viral biology and the outer limits of protein sequence and structure space.
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| 1. PSV 165a A 165aa protein with 2 homologous genes in the PSV genome. The structure is monomeric, with a conserved disulphide that is probably structurally stabilising. The winged helix domain highlighted in green is a good match to the RNA hairpin binding domain of the SelB protein and the Z-DNA binding domain of the dsRNA editing domain ADAR. We have shown that PSV165a binds DNA and RNA in vitro, and are currently following up these observations.
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| 2. PSV131. This protein forms a dimer in solution, with a bound zinc ion in each domain. The helix turn helix motif is suggestive of transcriptional regulator. We have confirmed the protein does bind dsDNA.
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| 3. SIRV 30 The protein has a novel fold and undergoes a very unusual helix swapping (the helix at the monomer interface swaps across the two fold). We observed this helix swapped.
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| 4. SIRV 21 Although a small protein (60 amino acids) gel filtration suggested the protein was an oligomer. Structure solution shows it is a hexamer (crystal symmetry is cubic). The central barrel is too small to thread DNA however, the external surface is positively charged. We are investigating to ascertain whether the protein binds DNA.
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| 5. PSV239. This 239aa protein has one sequence homologue in the database from a related archaeal virus. The C-terminal domain of the protein crystallised, yielding novel α-helical fold. Conserved residues, highlighted in magenta, include many aromatic residues on the surface of the protein – another unusual feature. This protein binds preferentially to dsDNA, although it shares no similarity with any known dsDNA binding protein. Further biochemical studies are underway.
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©Scottish Structural Proteomics Facility 2007.
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Updated:30-10-07 |
