title: Proline inhibits aggregation during protein refolding.
abstract: The in vitro refolding of hen egg-white lysozyme is studied in the presence of various osmolytes. Proline is found to prevent aggregation during protein refolding. However, other osmolytes used in this study fail to exhibit a similar property. Experimental evidence suggests that proline inhibits protein aggregation by binding to folding intermediate(s) and trapping the folding intermediate(s) into enzymatically inactive, "aggregation-insensitive" state(s). However, elimination of proline from the refolded protein mixture results in significant recovery of the bacteriolytic activity. At higher concentrations (>1.5 M), proline is shown to form loose, higher-order molecular aggregate(s). The supramolecular assembly of proline is found to possess an amphipathic character. Formation of higher-order aggregates is believed to be crucial for proline to function as a protein folding aid. In addition to its role in osmoregulation under water stress conditions, the results of this study hint at the possibility of proline behaving as a protein folding chaperone.
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: D
authors.initials: D
authors.lastname: Samuel
authors.forename: T K
authors.initials: TK
authors.lastname: Kumar
authors.forename: G
authors.initials: G
authors.lastname: Ganesh
authors.forename: G
authors.initials: G
authors.lastname: Jayaraman
authors.forename: P W
authors.initials: PW
authors.lastname: Yang
authors.forename: M M
authors.initials: MM
authors.lastname: Chang
authors.forename: V D
authors.initials: VD
authors.lastname: Trivedi
authors.forename: S L
authors.initials: SL
authors.lastname: Wang
authors.forename: K C
authors.initials: KC
authors.lastname: Hwang
authors.forename: D K
authors.initials: DK
authors.lastname: Chang
authors.forename: C
authors.initials: C
authors.lastname: Yu
mesh_terms: D000818:Animals; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D009113:Muramidase / Q000737:chemistry / Q000302:isolation & purification; D010084:Oxidation-Reduction; D011392:Proline / Q000494:pharmacology*; D011489:Protein Denaturation; D017510:Protein Folding; D013050:Spectrometry, Fluorescence
chemical_list: D046911:Macromolecular Substances; D011392:Proline; D009113:Muramidase