Irreversible formation of intermediate BSA oligomers requires and induces conformational changes

S. M. Vaiana, A. Emanuele, M. B. Palma-Vittorelli, M. U. Palma

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Understanding the relation between protein conformational changes and aggregation, and the physical mechanisms leading to such processes, is of primary importance, due to its direct relation to a vast class of severe pathologies. Growing evidence also suggests that oligomeric intermediates, which may occur early in the aggregation pathway, can be themselves pathogenic. The possible cytotoxicity of oligomers of non-disease-associated proteins adds generality to such suggestion and to the interest of studies of oligomer formation. Here we study the early stages of aggregation of Bovine Serum Albumin (BSA), a non pathogenic protein which has proved to be a useful model system. Dynamic light scattering and circular dichroism measurements in kinetic experiments following step-wise temperature rises, show that the "intermediate" form, which initiates large-scale aggregation, is the result of structural and conformational changes and concurrent formation of oligomers, of average size in the range of 100-200 Å. Two distinct thresholds are observed. Beyond the first one oligomerization starts and causes partial irreversibility of conformational changes. Beyond the second threshold, additional secondary structural changes occurring in proteins being recruited progress on the same time scale of oligomerization. The concurrent behavior causes a mutual stabilization of oligomerization, and of structural and conformational changes, evidenced by a progressive increase of their irreversibility. This process interaction appears to be pivotal in producing irreversible oligomers.

Original languageEnglish (US)
Pages (from-to)1053-1062
Number of pages10
JournalProteins: Structure, Function and Genetics
Volume55
Issue number4
DOIs
StatePublished - Apr 1 2004
Externally publishedYes

Keywords

  • Aggregation kinetics
  • Amyloid
  • Amyloidoses
  • Bovine Serum Albumin
  • Fibrils
  • Neurodegenerative diseases
  • Prions
  • Protein aggregation
  • Protein fibers
  • Recruitment

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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