HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gaur, N. K. Articles by Klotz, S. A. Search for Related Content PubMed PubMed Citation Articles by Gaur, N. K. Articles by Klotz, S. A. Agricola Articles by Gaur, N. K. Articles by Klotz, S. A.

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

¹ Research Service, University of Arizona, Tucson, AZ, USA
² Southern AZ VA Healthcare System and Department of Medicine, University of Arizona, Tucson, AZ, USA

Correspondence
Stephen A. Klotz
sklotz{at}u.arizona.edu

Candida albicans displays a high degree of specificity in selecting and adhering to targets in vivo. 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 C. albicans, henceforth referred to as SRS (stable, reversible, specific) adherence. It was previously demonstrated that C. albicans and Saccharomyces cerevisiae 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 C. albicans and S. cerevisiae expressing Als5p. C. albicans 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.

This article has been cited by other articles:

				H. N. Otoo, K. G. Lee, W. Qiu, and P. N. Lipke Candida albicans Als Adhesins Have Conserved Amyloid-Forming Sequences Eukaryot. Cell, May 1, 2008; 7(5): 776 - 782. [Abstract] [Full Text] [PDF]

				L. M. Douglas, L. Li, Y. Yang, and A. M. Dranginis Expression and Characterization of the Flocculin Flo11/Muc1, a Saccharomyces cerevisiae Mannoprotein with Homotypic Properties of Adhesion Eukaryot. Cell, December 1, 2007; 6(12): 2214 - 2221. [Abstract] [Full Text] [PDF]

				A. M. Dranginis, J. M. Rauceo, J. E. Coronado, and P. N. Lipke A Biochemical Guide to Yeast Adhesins: Glycoproteins for Social and Antisocial Occasions Microbiol. Mol. Biol. Rev., June 1, 2007; 71(2): 282 - 294. [Abstract] [Full Text] [PDF]

				C. Wang and R. J. St Leger The MAD1 Adhesin of Metarhizium anisopliae Links Adhesion with Blastospore Production and Virulence to Insects, and the MAD2 Adhesin Enables Attachment to Plants Eukaryot. Cell, May 1, 2007; 6(5): 808 - 816. [Abstract] [Full Text] [PDF]

				J. M. Rauceo, R. De Armond, H. Otoo, P. C. Kahn, S. A. Klotz, N. K. Gaur, and P. N. Lipke Threonine-Rich Repeats Increase Fibronectin Binding in the Candida albicans Adhesin Als5p Eukaryot. Cell, October 1, 2006; 5(10): 1664 - 1673. [Abstract] [Full Text] [PDF]

				C. A. Munro, S. Bates, E. T. Buurman, H. B. Hughes, D. M. MacCallum, G. Bertram, A. Atrih, M. A. J. Ferguson, J. M. Bain, A. Brand, et al. Mnt1p and Mnt2p of Candida albicans Are Partially Redundant {alpha}-1,2-Mannosyltransferases That Participate in O-Linked Mannosylation and Are Required for Adhesion and Virulence J. Biol. Chem., January 14, 2005; 280(2): 1051 - 1060. [Abstract] [Full Text] [PDF]

				S. A. Klotz, N. K. Gaur, J. Rauceo, D. F. Lake, Y. Park, K. S. Hahm, and P. N. Lipke Inhibition of Adherence and Killing of Candida albicans with a 23-Mer Peptide (Fn/23) with Dual Antifungal Properties Antimicrob. Agents Chemother., November 1, 2004; 48(11): 4337 - 4341. [Abstract] [Full Text] [PDF]

				S. A. Klotz, N. K. Gaur, D. F. Lake, V. Chan, J. Rauceo, and P. N. Lipke Degenerate Peptide Recognition by Candida albicans Adhesins Als5p and Als1p Infect. Immun., April 1, 2004; 72(4): 2029 - 2034. [Abstract] [Full Text] [PDF]