title: Oxidation enhances human serum albumin thermal stability and changes the routes of amyloid fibril formation.
abstract: Oxidative damages are linked to several aging-related diseases and are among the chemical pathways determining protein degradation. Specifically, interplay of oxidative stress and protein aggregation is recognized to have a link to the loss of cellular function in pathologies like Alzheimer's and Parkinson's diseases. Interaction between protein and reactive oxygen species may indeed induce small changes in protein structure and lead to the inhibition/modification of protein aggregation process, potentially determining the formation of species with different inherent toxicity. Understanding the temperate relationship between these events can be of utmost importance in unraveling the molecular basis of neurodegeneration. In this work, we investigated the effect of hydrogen peroxide oxidation on Human Serum Albumin (HSA) structure, thermal stability and aggregation properties. In the selected conditions, HSA forms fibrillar aggregates, while the oxidized protein undergoes aggregation via new routes involving, in different extents, specific domains of the molecule. Minute variations due to oxidation of single residues affect HSA tertiary structure leading to protein compaction, increased thermal stability, and reduced association propensity.
authors.affiliation: Dipartimento di Fisica e Chimica, Universita' di Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sancataldo
authors.affiliation: Dipartimento di Fisica e Chimica, Universita' di Palermo, Palermo, Italy ; Consiglio Nazionale delle Ricerche-IBF u.o. Palermo, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Vetri
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark ; Sector of Biological and Soft Systems, Department of Physics, Cavendish Laboratory, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Vito
authors.initials: V
authors.lastname: Foderà
authors.affiliation: Centro di Oncobiologia Sperimentale, Palermo, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Di Cara
authors.affiliation: Dipartimento di Fisica e Chimica, Universita' di Palermo, Palermo, Italy ; Consiglio Nazionale delle Ricerche-IBF u.o. Palermo, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Militello
authors.affiliation: Dipartimento di Fisica e Chimica, Universita' di Palermo, Palermo, Italy ; Consiglio Nazionale delle Ricerche-IBF u.o. Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D010084:Oxidation-Reduction / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D013696:Temperature
chemical_list: D000682:Amyloid; D012709:Serum Albumin; D006861:Hydrogen Peroxide