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Volume 150, Issue 2

Accessibility of the peptide backbone of protein ligands is a key specificity determinant in SRS adherence Free

Abstract

displays a high degree of specificity in selecting and adhering to targets . The features of target recognition are poorly understood and likely to involve more than the mere chemical composition of the ligand. Using an adherence assay in which protein and peptide ligands are covalently coupled to magnetic beads, the authors have previously described a new adherence mechanism in , henceforth referred to as SRS (stable, reversible, specific) adherence. It was previously demonstrated that and expressing agglutinin-like sequence 5 protein (Als5p, previously referred to as Ala1p or Ala1/Als5p) adhere to peptides containing patches of threonine, serine and alanine residues when these are located in the free end of immobilized peptides. The interaction with protein ligands in SRS adherence predominantly involves the formation of hydrogen bonds. Accordingly, this interaction may occur (1) to the peptide backbone of the protein ligand or (2) to the amino acid side chain with an appropriate functional group. Evidence is provided that the primary interaction occurs with the peptide backbone and the secondary interaction occurs with the side chain. The primary interaction with the peptide backbone is sufficient for adherence to occur, whereas the secondary interaction with a side chain possessing an appropriate functional group stabilizes the interaction. In agreement with these results, it is also demonstrated that proteins lacking secondary and tertiary structure, wherein the peptide backbone is sterically accessible, interact with and expressing Als5p. Als proteins are resistant to denaturation by harsh conditions that kill the yeast cells. The proposed interactions in SRS adherence have striking similarities with those of the molecular chaperone Hsp70, which specifically binds to non-native proteins and resists denaturation.

  • Received:
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  • Published Online:
Keyword(s): CM, carboxylate modified , dFN, denatured fibronectin , dLM, denatured laminin , FN, fibronectin , LM, laminin , SRS, stable, reversible, specific (adherence) and TA, tosyl activated
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2004-02-01
2024-04-19
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References

  1. Calderone R. A., Braun P. C. 1991; Adherence and receptor relationships of Candida albicans . Microbiol Rev 55:1–20
     [Google Scholar]
  2. Casadevall A., Pirofski L. 2000; Host-pathogen interactions: basic concepts of microbial commensalism, colonization, infection, and disease. Infect Immun 68:6511–6518 [CrossRef]
     [Google Scholar]
  3. Fu Y., Rieg G., Fonzi W. A., Belanger P. H., Edwards J. E., Filler S. G. 1998; Expression of the Candida albicans gene ALS1 in Saccharomyces cerevisiae induces adherence to endothelial and epithelial cells. Infect Immun 66:1783–1786
     [Google Scholar]
  4. Gaur N. K., Klotz S. A. 1997; Expression, cloning, and characterization of a Candida albicans gene, ALA1 , that confers adherence properties upon Saccharomyces cerevisiae for extracellular matrix proteins. Infect Immun 65:5289–5294
     [Google Scholar]
  5. Gaur N., Klotz S., Henderson R. 1999; Overexpression of the Candida albicans ALA1 gene in Saccharomyces cerevisiae results in aggregation following attachment of yeast cells to extracellular matrix proteins, adherence properties similar to those of Candida albicans . Infect Immun 67:6040–6047
     [Google Scholar]
  6. Gaur N. K., Smith R. L., Klotz S. A. 2002; Candida albicans and Saccharomyces cerevisiae expressing ALA1/ALS5 adhere to accessible threonine, serine or alanine patches. Cell Commun Adhes 9:45–57 [CrossRef]
     [Google Scholar]
  7. Hartl F. U., Hayer-Hartl M. 2002; Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858 [CrossRef]
     [Google Scholar]
  8. Hoyer L. L. 2001; The ALS gene family of Candida albicans. Trends Microbiol 9:176–180 [CrossRef]
     [Google Scholar]
  9. Hube B., Naglik J. 2001; Candida albicans proteinases: resolving the mystery of a gene family. Microbiology 147:1997–2005
     [Google Scholar]
  10. Hube B., Stehr F., Bossenz M., Mazur A., Kretschmar M., Schafer W. 2000; Secreted lipases of Candida albicans : cloning, characterisation and expression analysis of a new gene family with at least ten members. Arch Microbiol 174:362–374 [CrossRef]
     [Google Scholar]
  11. Klotz S. A., Smith R. L. 1995; Gelatin fragments block adherence of Candida albicans to extracellular matrix proteins. Microbiology 141:2681–2684 [CrossRef]
     [Google Scholar]
  12. Klotz S. A., Drutz D. J., Harrison J. L., Huppert M. 1983; Adherence and penetration of vascular endothelium by Candida yeasts. Infect Immun 42:374–384
     [Google Scholar]
  13. Naglik J. R., Challacombe S. J., Hube B. 2003; Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol Mol Biol Rev 67:400–428 [CrossRef]
     [Google Scholar]
  14. Pendrak M. L., Klotz S. A. 1995; Adherence of Candida albicans to host cells. FEMS Microbiol Lett 129:103–114
     [Google Scholar]
  15. Soll D. R. 2002; Candida commensalism and virulence: the evolution of phenotypic plasticity. Acta Trop 81:101–110 [CrossRef]
     [Google Scholar]
  16. Stabb J. F., Bradway S. D., Fidel P. L., Sundstrom P. 1999; Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science 283:1535–1537 [CrossRef]
     [Google Scholar]
  17. Sundstrom P. 2002; Adhesion in Candida spp. Cell Microbiol 4:461–469 [CrossRef]
     [Google Scholar]
  18. Van Burik J. H., Magee P. T. 2001; Aspects of fungal pathogenesis in humans. Annu Rev Microbiol 55:743–772 [CrossRef]
     [Google Scholar]
  19. Zhu X., Zhao X., Burkholder W. F., Gragerov A., Ogata C. M., Gottesman M. E., Hendrickson W. A. 1996; Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272:1606–1614 [CrossRef]
     [Google Scholar]
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Accessibility of the peptide backbone of protein ligands is a key specificity determinant in Candida albicans SRS adherence
Microbiology 150, 277 (2004); https://doi.org/10.1099/mic.0.26738-0
/content/journal/micro/10.1099/mic.0.26738-0
/content/journal/micro/10.1099/mic.0.26738-0
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