Premium
The C‐Terminus of the β Protein is Critical in Amyloidogenesis a
Author(s) -
JARRETT JOSEPH T.,
BERGER ELIZABETH P.,
LANSBURY PETER T.
Publication year - 1993
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1993.tb23043.x
Subject(s) - chemistry , fibril , senile plaques , amyloid fibril , amyloid (mycology) , biophysics , peptide , nucleation , residue (chemistry) , extracellular , protein aggregation , biochemistry , protein secondary structure , n terminus , protein structure , peptide sequence , amyloid β , alzheimer's disease , biology , medicine , organic chemistry , disease , inorganic chemistry , gene
The β amyloid protein found in extracellular deposits in Alzheimer's disease (AD) is heterogeneous at its C‐terminus; proteins ending at residues 40, 42, and 43 have been identified in neuritic deposits, while protein in vascular amyloid appears to end at residue 39 or 40. Studies of synthetic β proteins (β1–39, β1–40, β1–42), and model peptides (β26–39, β26–40, β26–42, β26–43) demonstrate that amyloid formation is a nucleation‐dependent phenomenon. Peptides ending at residues 39 or 40 were kinetically soluble for hours to days, while peptides ending at residues 42 or 43 aggregated immediately; all eventually reached similar thermodynamic solubility. The kinetically soluble variants could be seeded with the kinetically insoluble variants. The secondary structure of β26–39 fibrils was different from that of β26–42 fibrils, however, seeding β26–39 with β26–42 produces mixed fibrils with structure similar to β26–42. These results suggest that neuritic plaques may be seeded by their minor component; this may determine the structure and properties of amyloid in AD.