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The Open Protein Structure Annotation Network
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PSfold

    Table of contents
    1. 1. Summary
    2. 2. Credits
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    Alternative Viewpoints

     

    Summary

     

    The Joint Center for Structural Genomics (JCSG) has determined structural representatives of a novel, functionally uncharacterized protein family as part of the Protein Structure Initiative (PSI) mandate to explore unchartered territories of protein sequence/structural space. SPO0140 from Silicibacter pomeroyi DSS-3 (PDB id: 2re3) and Sbal_2486 from Shewanella baltica (PDB id: 2ra9) are the first proteins of Pfam family PF06938 (DUF1285) to have their structures determined. Routine sequence analysis reveals around 200 members in the DUF1285 family that vary between 150-250 residues in length. Structural analyses indicate that SPO0140 and Sbal_2486 are likely monomers that comprise two domains with a conserved core suggestive of gene duplication and display variability at N- and C-terminal ends. Remote structural similarity to members of the SH3-like and the PH-like folds is observed. Careful sequence and structural analyses allow us to extend the limits of the DUF1285 family (>300 homologs) to include a group of eukaryotic homologs (UPF0598, ~40 homologs) and a divergent bacterial group (~65 homologs) with distinct sequence conservation patterns. Our analysis helps resolve questions relating to the classification of these structures as a new fold that is evolutionarily distinct from the structurally similar PH-like and SH3-like folds. Three distinct functional hypotheses, viz., head-to-tail, filament-like polymeric association; possible enzymatic activity reminiscent of a peptidase/esterase-like function (for the eukaryotic homologs); and a likely involvement of DUF1285 proteins in DNA oxidative repair are suggested.

    Credits

    The credits listed below involve only structural, evolutionary and functional analyses of the DUF1285 family. For credits relating to the structure determination of PDB ids 2RE3 and 2RA9, please see the relevant individual TOPSAN pages and manuscript submitted to Acta F. The latter is entitled "Crystal structures of the first representatives of Pfam family PF06938 (DUF1285) reveal a new fold with repeated structural motifs and suggest an involvement in signal transduction".

     

    Krishna: N- and C-terminal domains related by duplication.

    See Discussions for more details.

     

    Alexey and Tony: classified both DUF1285 domains as a single folding unit; identified beta3-alpha-beta3 unit as ancestral fold; proposed polymer-like model for DUF1285 family and identified conserved motifs implicated in polymerization; proposed a cytoskeletal role for the DUF1285 family which would involve formation of linear polymers that might act as scaffold for binding other molecules; suggest different functionalities between DUF1285 and eukaryotic orthologs (see below).

    See Alexey's and Tony's page and Discussions for more information on the analysis.

     

    Nick: extended DUF1285 homology to include eukaryotic (UPF0598) and more remote bacterial families; built homology model form human homolog (CH082_HUMAN); identified relationships between families; identified minimal repeating units in DUF1285 fold' illustrated relationships between different known folds and DUF1285 fold and presents evolutionary hypotheses about origin of beta barrels; suggested a regulatory role for DUF1285 with primary function involving binding to nucleic acids or other proteins.

    See Nick's page and Discussions for more information on the analysis.

     

    Aravind: confirmed link of eukaryotic to prokaryotic DUF1285 homologs; identified possible catalytic triad in eukaryotic group reminiscent of a peptidase/esterase-like function; identified cytosine deaminase match using profile-profile comparisons. This link would suggest a function in pyrimidine metabolism.

    See Discussions for more details of Aravind's analysis.

     

    Tina: proposed signaling function for DUF1285 group, likely involving binding to a nucleotide-based second messenger under conditions of oxidative stress.

    See Discussions for more details.

    Reviews

    References

     

    No references found.

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