title: Degenerate peptide recognition by Candida albicans adhesins Als5p and Als1p.
abstract: Candida albicans and Saccharomyces cerevisiae expressing the adhesins Als5p or Als1p adhere to immobilized peptides and proteins that possess appropriate sequences of amino acids in addition to a sterically accessible peptide backbone. In an attempt to further define the nature of these targets, we surveyed the ability of yeast cells to adhere to 90- micro m-diameter polyethylene glycol beads coated with a 7-mer peptide from a library of 19(7) unique peptide-beads. C. albicans bound to ca. 10% of beads from the library, whereas S. cerevisiae expressing Als5p or Als1p bound to ca. 0.1 to 1% of randomly selected peptide-beads. S. cerevisiae expressing Als1p had a distinctly different adherence phenotype than did cells expressing Als5p. The former adhered in groups or clumps of cells, whereas the latter adhered initially as single cells, an event which was followed by the build up of cell-cell aggregates. Beads with adherent cells were removed, and the peptide attached to the bead was determined by amino acid sequencing. All adhesive beads carried a three-amino-acid sequence motif (tau phi+) that possessed a vast combinatorial potential. Adherence was sequence specific and was inhibited when soluble peptide identical to the immobilized peptide was added. The Als5p adhesin recognized some peptides that went unrecognized by Als1p. The sequence motif of adhesive peptides identified by this method is common in proteins and offers so many possible sequence combinations that target recognition by the Als proteins is clearly degenerate. A degenerate recognition system provides the fungi with the potential of adhering to a multitude of proteins and peptides, an advantage for any microorganism attempting to establish a commensal or pathogenic relationship with a host.
authors.affiliation: Department of Medicine, University of Arizona and Southern Arizona VA Health Care System, Tucson, Arizona 85724, USA.sklotz@u.arizona.edu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Klotz
authors.forename: Nand K
authors.initials: NK
authors.lastname: Gaur
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Lake
authors.forename: Vincent
authors.initials: V
authors.lastname: Chan
authors.forename: Jason
authors.initials: J
authors.lastname: Rauceo
authors.forename: Peter N
authors.initials: PN
authors.lastname: Lipke
mesh_terms: D000595:Amino Acid Sequence; D002176:Candida albicans / Q000378:metabolism*; D002448:Cell Adhesion; D005656:Fungal Proteins / Q000378:metabolism*; D008024:Ligands; D008863:Microspheres; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols; D012680:Sensitivity and Specificity
chemical_list: C093538:ALS1 protein, Candida albicans; D005656:Fungal Proteins; D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D011092:Polyethylene Glycols