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The baker’s yeast Saccharomyces cerevisiae harbors a set of cell wall an-chored proteins that confer cell-cell or cell-surface Interactions. These proteins called flocculins or adhesins share a common architecture consisting of an A-, B- and C-domain with the A-domain responsible for substrate binding. The ad-hesins can be divided into two independent groups, the PA14-type and the Flo11-type. The PA14-type contains the flocculins Flo1, Flo5, Flo9, Flo10 and these proteins have a central PA14 domain as core structure. The Flo11-type forms an own Pfam family (PF10182) und shows no homology to the PA14-type. The Flo11-dependent phenotypes in Saccharomyces cerevisiae show a great diversity (biofilms, flocculation, flor formation, filaments), but with adhesion to cells or surfaces as connecting element. In this work the crystal structures of the Flo11A domains from S. cerevisiae (ScFlo11A) and K. pastoris GS115 (KpFlo11A1) could be solved. Although these two Flo11A domains share a sequence identity of only 30 %, the 3D structure is highly conserved with a Fibronectin type III domain as core structure. In comparison to the flocculins of the PA14-type the Flo11A domain doesn’t bind any sugar moieties but confers homotypic Flo11A-Flo11A interactions via surface exposed aromatic residues (tryptophan and tyrosin). These aromatic residues are embedded into groups of acidic residues, namely aspartate and glutamate. Hence a homotypic interaction can only occur when both domains are almost uncharged. The resulting pH-dependence of the interaction forms the molecular basis for cell-cell adhesion of yeasts under acidic conditions. At pH 5.5 a KD value of 20 µM for the ScFlo11A-ScFlo11A interaction and 30 µM for the KpFlo11A1-KpFlo11A1 interaction could be delineated by Surface Plasmon Resonance (SPR). The heterotypic ScFlo11A-KpFlo11A interaction showed a KD of 121 µM. The reason for this reduced affinity was mainly due to a slower association (kon) while the dissociation (koff) was almost unaffected. This work could help elucidating the unusual adhesion mechanism of the Flo11A-Flo11A interaction by combining structural and biophysical methods.