The structural and functional characteristics of a yeast alcohol dehydrogenase (ADH) peptide (YSGVCHTDLHAWHGD WPLPVK, residues 40-60) have been studied in detail. The peptide is hydrophobic in nature, binds the hydrophobic probe bis-ANS, and is mostly present in a random coil conformation. It shows chaperone-like activity by preventing dithiothreitol (DTT)-induced aggregation of insulin at 27 degreesC, oxidation-induced aggregation of gamma-crystallin at 37 degreesC, and aggregation of thermally denatured ADH and beta(L)-crystallins at 52 degreesC. However, the ADH peptide does not solubilize protein aggregates as do surfactants. Substitution of Pro for His in the ADH peptide leads to diminished anti-aggregation activity. Further, analysis of ADH incubated at 47degreesC suggests that a significant portion of the enzyme remains as soluble inactive protein with negligible conformational change. Therefore, we propose that the residues 40-60 in native protein may be an intramolecular chaperone site of yeast ADH. (C) 2003 Elsevier Science (USA). All rights reserved.