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

The yeast cell adhesion protein cr-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 alpha -agglutinin has a beta -sheet-rich structure, with only similar to2% alpha -helix under native conditions (15-40 degreesC 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 similar to 17% of the residues have high alpha -helical and low beta -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 alpha -agglutinin showed reversible conversion from beta -rich to mixed alpha/beta 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-beta and the alpha/beta 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 beta -rich state by covalent and local charge interactions under native conditions, but form helices under non-native conditions.