skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

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 ({approx}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 10{sup 20} 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.

Authors:
;  [1]
  1. (UCSD)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1041342
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. USA
Additional Journal Information:
Journal Volume: 108; Journal Issue: (35) ; 08, 2011; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; CRYSTALLOGRAPHY; ENZYMES; LECTINS; PROTEINS; RESIDUES; VERTEBRATES

Citation Formats

Le Coq, Johanne, and Ghosh, Partho. Conservation of the C-type lectin fold for massive sequence variation in a Treponema diversity-generating retroelement. United States: N. p., 2012. Web. doi:10.1073/pnas.1105613108.
Le Coq, Johanne, & Ghosh, Partho. Conservation of the C-type lectin fold for massive sequence variation in a Treponema diversity-generating retroelement. United States. doi:10.1073/pnas.1105613108.
Le Coq, Johanne, and Ghosh, Partho. Tue . "Conservation of the C-type lectin fold for massive sequence variation in a Treponema diversity-generating retroelement". United States. doi:10.1073/pnas.1105613108.
@article{osti_1041342,
title = {Conservation of the C-type lectin fold for massive sequence variation in a Treponema diversity-generating retroelement},
author = {Le Coq, Johanne and Ghosh, Partho},
abstractNote = {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 ({approx}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 10{sup 20} 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.},
doi = {10.1073/pnas.1105613108},
journal = {Proc. Natl. Acad. Sci. USA},
issn = {0027-8424},
number = (35) ; 08, 2011,
volume = 108,
place = {United States},
year = {2012},
month = {6}
}