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Abstract

In mice, amyloidogenic type C apolipoprotein A-II (apoA-II) forms amyloid fibrils in age-associated amyloidosis. To understand the mechanism of amyloid fibril formation by apoA-II, we examined the polymerization of synthetic partial peptides of apoA-II in vitro. None of the partial apoA-II peptides polymerized into amyloid fibrils when tested as a single species mixture. We found a unique mechanism in which N- and C-terminal peptides associated into amyloid fibrils in a 1:1 ratio at pH 2.5. The 11-residue amino acid sequence (6-16), which is a common sequence of type B apoA-II and type C apoA-II proteins in amyloidosis-resistant mice and amyloidosis-susceptible mice, respectively, was critical for polymerization into amyloid fibrils. The 18-residue-long amino acid sequence (48-65) is also necessary for nucleation, but not for the extension phase. These findings suggest that there may be different mechanisms underlying the nucleation and extension phases of apoA-II amyloid fibril formation. We also found that amino acid substitutions between type B apoA-II (Pro5, Val38) and type C apoA-II (Gln5, Ala38) did not affect either phase. The strategy of using synthetic partial peptides of amyloidogenic proteins in vitro is a useful system for understanding amyloid fibril formation and for the development of novel therapies.

Journal

  • BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

    BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 1794(10), 1517-1529, 2009-10

    ELSEVIER SCIENCE BV

Codes

  • NII Article ID (NAID)
    120002598959
  • NII NACSIS-CAT ID (NCID)
    AA11685085
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    1570-9639
  • Data Source
    IR 
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