A Biochemical Guide to Yeast Adhesins: Glycoproteins for Social and Antisocial Occasions

Abstract

SUMMARY Fungi are nonmotile eukaryotes that rely on their adhesins for selective interaction with the environment and with other fungal cells. Glycosylphosphatidylinositol (GPI)-cross-linked adhesins have essential roles in mating, colony morphology, host-pathogen interactions, and biofilm formation. We review the structure and binding properties of cell wall-bound adhesins of ascomycetous yeasts and relate them to their effects on cellular interactions, with particular emphasis on the agglutinins and flocculins of Saccharomyces and the Als proteins of Candida. These glycoproteins share common structural motifs tailored to surface activity and biological function. After being secreted to the outer face of the plasma membrane, they are covalently anchored in the wall through modified GPI anchors, with their binding domains elevated beyond the wall surface on highly glycosylated extended stalks. N-terminal globular domains bind peptide or sugar ligands, with between millimolar and nanomolar affinities. These affinities and the high density of adhesins and ligands at the cell surface determine microscopic and macroscopic characteristics of cell-cell associations. Central domains often include Thr-rich tandemly repeated sequences that are highly glycosylated. These domains potentiate cell-to-cell binding, but the molecular mechanism of such an association is not yet clear. These repeats also mediate recombination between repeats and between genes. The high levels of recombination and epigenetic regulation are sources of variation which enable the population to continually exploit new niches and resources.

Atomic force microscopy – looking at mechanosensors on the cell surface

“…Microscopic assays have revealed that Als-mediated adhesion involves an initial adhesion step, followed by force-induced protein conformational changes that result in the formation of strong amyloid-like bonds that can 'cement' the adhering cells together (Dranginis et al, 2007;Lipke et al, 2012). Again, the molecular details of this mechanism remained essentially unknown.…”

Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

“…Both groups contain GPI proteins. Cell wall proteins have been reviewed by Klis et al (2002, Lesage and Bussey (2006), and Gonzalez et al (2009), glycosylhydrolases by Adams (2004), agglutinins by Dranginis et al (2007), and flocculins by Goossens and Willaert (2010). Additional information about these proteins is presented in File S9.…”

“…The first contains those with the potential to participate in wall construction as hydrolases or transglycosidases. The second contains nonenzymatic agglutinins, flocculins, or b1,3-glucan cross-connectors (Klis et al , 2010Dranginis et al 2007;Goossens and Willaert 2010). Most, if not all the proteins in these two groups are glycosylated.…”

“…Flocculins and agglutinins: GPI-CWP involved in cell-cell adhesion are the related Flo1, Flo5, Flo9, Flo10, and Flo11/ Muc1 flocculins, the Aga1 and Fig2 pair, and the a-agglutinin Sag1 (Roy et al 1991;Cappellaro et al 1994;Chen et al 1995;Caro et al 1997;Erdman et al 1998;Guo et al 2000;Shen et al 2001;Dranginis et al 2007;Van Mulders et al 2009;Goossens and Willaert 2010).…”

Force-induced formation and propagation of adhesion nanodomains in living fungal cells

“…A remarkable trait of adhesion domains is their ability to grow and strengthen under force (8-10). Whether such force-dependent behavior also occurs with microbial adhesins is unknown.Adhesins in the Candida albicans Als gene family bind the pathogen to host tissues and initiate biofilm formation (11,12). Als proteins are covalently attached to the cell wall and consist of an N-terminal Ig-like region, which initiates cell adhesion, followed by a threonine-rich region with an amyloid-forming sequence (T), a tandem repeat (TR) region that participates in cellcell aggregation, and a stalk region projecting the molecule away from the cell surface (Fig.…”