Thermodynamic versus Conformational Metastability in Fibril-Forming Lysozyme Solutions (Articolo in rivista)

Type
Label
  • Thermodynamic versus Conformational Metastability in Fibril-Forming Lysozyme Solutions (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/jp303430g (literal)
Alternative label
  • Raccosta S; Martorana V; Manno M (2012)
    Thermodynamic versus Conformational Metastability in Fibril-Forming Lysozyme Solutions
    in The journal of physical chemistry. B; American Chemical Society, Washington (Stati Uniti d'America)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Raccosta S; Martorana V; Manno M (literal)
Pagina inizio
  • 12078 (literal)
Pagina fine
  • 12087 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://pubs.acs.org/doi/abs/10.1021/jp303430g (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 116 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 40 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Institute of Biophysics, National Research Council of Italy, via U. La Malfa 153, I-90146 Palermo, Italy; Dipartimento di Fisica, Università di Palermo, via Archirafi 36, I-90123 Palermo, Italy (literal)
Titolo
  • Thermodynamic versus Conformational Metastability in Fibril-Forming Lysozyme Solutions (literal)
Abstract
  • The role of intermolecular interaction in fibril-forming protein solutions and its relation with molecular conformation is a crucial aspect for the control and inhibition of amyloid structures. Here, we study the fibril formation and the protein-protein interactions of lysozyme at acidic pH and low ionic strength. The amyloid formation occurs after a long lag time and is preceded by the formation of oligomers, which seems to be off-pathway with respect to fibrillation. By measuring the osmotic isothermal compressibility and the collective diffusion coefficient of lysozyme in solution, we observe that the monomeric solution is kept in a thermodynamically metastable state by strong electrostatic repulsion, even in denaturing conditions. The measured repulsive interaction between monomers is satisfactorily accounted for by classical polyelectrolyte theory. Further, we observe a slow conformational change involving both secondary and tertiary structure, which drives the proteins toward a more hydrophobic conformation. Denatured proteins are driven out of metastability through conformational substates, which are kinetically populated and experience a lower activation energy for fibril formation. Thus, our results highlight the role of electrostatic repulsion, which hinders the aggregation of partially denatured proteins and operates as a gatekeeper favoring the association of those monomers whose conformation is capable of forming amyloid structure. (literal)
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