title: Classification of acid denaturation of proteins: intermediates and unfolded states.
abstract: A systematic investigation of the effect of acid on the denaturation of some 20 monomeric proteins indicates that several different types of conformational behavior occur, depending on the protein, the acid, the presence of salts or denaturant, and the temperature. Three major types of effects were observed. Type I proteins, when titrated with HCl in the absence of salts, show two transitions, initially unfolding in the vicinity of pH 3-4 and then refolding to a molten globule-like conformation, the A state, at lower pH. Two variations in this behavior were noted: some type I proteins, when titrated with HCl in the absence of salts, show only partial unfolding at pH 2 before the transition to the molten globule state; others of this class form an A state that is a less compact from of the molten globule state. In the presence of salts, these proteins transform directly from the native state to the molten globule conformation. Type II proteins, upon acid titration, do not fully unfold but directly transform to the molten globule state, typically in the vicinity of pH 3. Type III proteins show no significant unfolding to pH as low as 1, but may be caused to behave similarly to type I in the presence of urea. Thus, the exact behavior of a given protein at low pH is a complex interplay between a variety of stabilizing and destabilizing forces, some of which are very sensitive to the environment. In particular, the protein conformation is quite sensitive to salts (anions) that affect the electrostatic interactions, denaturants, and temperature, which cause additional global destabilization.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Chemistry, University of California, Santa Cruz 95064.
authors.forename: A L
authors.initials: AL
authors.lastname: Fink
authors.forename: L J
authors.initials: LJ
authors.lastname: Calciano
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.forename: T
authors.initials: T
authors.lastname: Kurotsu
authors.forename: D R
authors.initials: DR
authors.lastname: Palleros
mesh_terms: D000143:Acids; D002942:Circular Dichroism; D004563:Electrochemistry; D019791:Guanidine; D006146:Guanidines; D006851:Hydrochloric Acid; D006863:Hydrogen-Ion Concentration; D011189:Potassium Chloride; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000145:classification*; D013696:Temperature
chemical_list: D000143:Acids; D006146:Guanidines; D011506:Proteins; D011189:Potassium Chloride; D019791:Guanidine; D006851:Hydrochloric Acid