Environmentally induced reversible conformational switching in the yeast cell adhesion protein α‐agglutinin

The yeast cell adhesion protein α‐agglutinin is expressed on the surface of a free‐living organism and is subjected to a variety of environmental conditions. Circular dichroism (CD) spectroscopy shows that the binding region of α‐agglutinin has a β‐sheet‐rich structure, with only ∼2% α‐helix under native conditions (15–40°C at pH 5.5). This region is predicted to fold into three immunoglobulin‐like domains, and models are consistent with the CD spectra as well as with peptide mapping and site‐specific mutagenesis. However, secondary structure prediction algorithms show that segments comprising ∼17% of the residues have high α‐helical and low β‐sheet potential. Two model peptides of such segments had helical tendencies, and one of these peptides showed pH‐dependent conformational switching. Similarly, CD spectroscopy of the binding region of α‐agglutinin showed reversible conversion from β‐rich to mixed α/β structure at elevated temperatures or when the pH was changed. The reversibility of these changes implied that there is a small energy difference between the all‐β and the α/β states. Similar changes followed cleavage of peptide or disulfide bonds. Together, these observations imply that short sequences of high helical propensity are constrained to a β‐rich state by covalent and local charge interactions under native conditions, but form helices under non‐native conditions.