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

Citation
H. Zhao et al., Environmentally induced reversible conformational switching in the yeast cell adhesion protein alpha-agglutinin, PROTEIN SCI, 10(6), 2001, pp. 1113-1123
Citations number
59
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEIN SCIENCE
ISSN journal
0961-8368 → ACNP
Volume
10
Issue
6
Year of publication
2001
Pages
1113 - 1123
Database
ISI
SICI code
0961-8368(200106)10:6<1113:EIRCSI>2.0.ZU;2-T
Abstract
The yeast cell adhesion protein cr-agglutinin is expressed on the surface o f a free-living organism and is subjected to a variety of environmental con ditions. Circular dichroism (CD) spectroscopy shows that the binding region of alpha -agglutinin has a beta -sheet-rich structure, with only similar t o2% alpha -helix under native conditions (15-40 degreesC at pH 5.5). This r egion is predicted to fold into three immunoglobulin-like domains, and mode ls are consistent with the CD spectra as well as with peptide mapping and s ite-specific mutagenesis. However, secondary structure prediction algorithm s show that segments comprising similar to 17% of the residues have high al pha -helical and low beta -sheet potential. Two model peptides of such segm ents 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. T he reversibility of these changes implied that there is a small energy diff erence between the all-beta and the alpha/beta states. Similar changes foll owed cleavage of peptide or disulfide bonds. Together, these observations i mply that short sequences of high helical propensity are constrained to a b eta -rich state by covalent and local charge interactions under native cond itions, but form helices under non-native conditions.