title: Hydrophobic collapse overrides Coulombic repulsion in ferricytochrome c fibrillation under extremely alkaline condition.
abstract: Tuning of both hydrophobic and electrostatic interactions is thought to be important for the initial nucleation and stability of protein aggregates that self-assemble to produce amyloid fibrils. Importance of a critical balance of these two interactions has indeed been determined under various solution conditions of fibrillation, the acidic pH, in particular. To find out if fibrillar protein structures could be obtained under extreme alkaline conditions, cytochrome c was allowed to fibrillate in 0.1 N NaOH at 50 or 60 °C. Fibers do grow in alkali, but the fibrillation process depends little on the ionic strength of the solution. Illustrative fibril morphology readily obtained even in the absence of solvent cations poses the question as to how the severity of electrostatic repulsions is overcome to initiate aggregation. It appears that intermolecular hydrophobic collapse is so overwhelming that electrostatic repulsions are subdued, and the negative charges on protein molecules are relocated in a way conducive to fiber growth. This proposal seems consistent with computer simulation studies indicating central role of hydrophobic interactions. Morphologically, branched fibrils characterized by a wide distribution of diameter are assembled by winding two or more protofibrils. The results should guide selection of model parameters in theoretical studies of fibrillation.
authors.affiliation: School of Chemistry, University of Hyderabad, Hyderabad 500 046, India.
authors.forename: Dasari
authors.initials: D
authors.lastname: Ramakrishna
authors.forename: Muvva D
authors.initials: MD
authors.lastname: Prasad
authors.forename: Abani K
authors.initials: AK
authors.lastname: Bhuyan
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D006736:Horses; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D009994:Osmolar Concentration; D011487:Protein Conformation; D011489:Protein Denaturation; D012972:Sodium Hydroxide / Q000378:metabolism; D055672:Static Electricity
chemical_list: D000682:Amyloid; D012972:Sodium Hydroxide; D045304:Cytochromes c