Conservation of the C-type lectin fold for massive sequence variation in a Treponema diversity-generating retroelement

Anticipatory ligand binding through massive protein sequence variation is rare in biological systems, having been observed only in the vertebrate adaptive immune response and in a phage diversity-generating retroelement (DGR). Earlier work has demonstrated that the prototypical DGR variable protein,...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-08, Vol.108 (35), p.14649-14653
Main Authors: Le Coq, Johanne, Ghosh, Partho
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Adaptive Immunity
Bacteria
Bacterial proteins
Bacterial Proteins - chemistry
Bacteriophages
BASIC BIOLOGICAL SCIENCES
Binding sites
Biofilms
Biological Sciences
Bordetella
CRYSTALLOGRAPHY
ENZYMES
Gram-negative bacteria
Immune response
LECTINS
Lectins, C-Type - chemistry
Ligands
Protein Folding
PROTEINS
RESIDUES
Retroelements
Retrotransposons
sequence analysis
Treponema
Treponema - genetics
Treponema denticola
VERTEBRATES
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Summary:Anticipatory ligand binding through massive protein sequence variation is rare in biological systems, having been observed only in the vertebrate adaptive immune response and in a phage diversity-generating retroelement (DGR). Earlier work has demonstrated that the prototypical DGR variable protein, major tropism determinant (Mtd), meets the demands of anticipatory ligand binding by novel means through the C-type lectin (CLec) fold. However, because of the low sequence identity among DGR variable proteins, it has remained unclear whether the CLec fold is a general solution for DGRs. We have addressed this problem by determining the structure of a second DGR variable protein, TvpA, from the pathogenic oral spirochete Treponema denticola. Despite its weak sequence identity to Mtd (∼16%), TvpA was found to also have a CLec fold, with predicted variable residues exposed in a ligand-binding site. However, this site in TvpA was markedly more variable than the one in Mtd, reflecting the unprecedented approximate 1020 potential variability of TvpA. In addition, similarity between TvpA and Mtd with formylglycine-generating enzymes was detected. These results provide strong evidence for the conservation of the formylglycine-generating enzyme-type CLec fold among DGRs as a means of accommodating massive sequence variation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1105613108