title: Environmentally induced reversible conformational switching in the yeast cell adhesion protein alpha-agglutinin.
abstract: The yeast cell adhesion protein alpha-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 approximately 2% alpha-helix under native conditions (15-40 degrees 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 approximately 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.
authors.affiliation: Department of Biological Sciences and the Institute for Biomolecular Structure and Function, Hunter College of the City University of New York, New York 10021,USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: M H
authors.initials: MH
authors.lastname: Chen
authors.forename: Z M
authors.initials: ZM
authors.lastname: Shen
authors.forename: P C
authors.initials: PC
authors.lastname: Kahn
authors.forename: P N
authors.initials: PN
authors.lastname: Lipke
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002942:Circular Dichroism; D004220:Disulfides; D004777:Environment; D006863:Hydrogen-Ion Concentration; D007136:Immunoglobulins / Q000737:chemistry; D000072235:Mating Factor; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010449:Peptide Mapping; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013696:Temperature; D014466:Ultraviolet Rays
chemical_list: D004220:Disulfides; D007136:Immunoglobulins; D010455:Peptides; D000072235:Mating Factor