Threonine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p

Jason M. Rauceo, Richard De Armond, Henry Otoo, Peter C. Kahn, Stephen A. Klotz, Nand K. Gaur, Peter N. Lipke

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80 Scopus citations

Abstract

Commensal and pathogenic states of Candida albicans depend on cell surface-expressed adhesins, including those of the Als family. Mature Als proteins consist of a 300-residue N-terminal region predicted to have an immunoglobulin (Ig)-like fold, a 104-residue conserved Thr-rich region (T), a central domain of a variable number of tandem repeats (TR) of a 36-residue Thr-rich sequence, and a heavily glycosylated C-terminal Ser/Thr-rich stalk region, also of variable length (N. K. Gaur and S. A. Klotz, Infect. Immun. 65: 5289-5294, 1997). Domain deletions in ALS5 were expressed in Saccharomyces cerevisiae to excrete soluble protein and for surface display. Far UV circular dichroism indicated that soluble Ig-T showed a single negative peak at 212 nm, consistent with previous data indicating that this region has high β-sheet content with very little α-helix. A truncation of Als5p with six tandem repeats (Ig-T-TR6) gave spectra with additional negative ellipticity at 200 nm and, at 227 to 240 nm, spectra characteristic of a structure with a similar fraction of β-sheet but with additional structural elements as well. Soluble Als5p Ig-T and Ig-T-TR6 fragments bound to fibronectin in vitro, but the inclusion of the TR region substantially increased affinity. Cellular adhesion assays with S. cerevisiae showed that the Ig-T domain mediated adherence to fibronectin and that TR repeats greatly increased cell-to-cell aggregation. Thus, the TR region of Als5p modulated the structure of the Ig-T region, augmented cell adhesion activity through increased binding to mammalian ligands, and simultaneously promoted fungal cell-cell interactions.

Original languageEnglish (US)
Pages (from-to)1664-1673
Number of pages10
JournalEukaryotic Cell
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2006

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Rauceo, J. M., De Armond, R., Otoo, H., Kahn, P. C., Klotz, S. A., Gaur, N. K., & Lipke, P. N. (2006). Threonine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p. Eukaryotic Cell, 5(10), 1664-1673. https://doi.org/10.1128/EC.00120-06