NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded

Biochemistry. 1996 Oct 29;35(43):13709-15. doi: 10.1021/bi961799n.


The "non-A beta component of Alzheimer's disease amyloid plaque" (NAC) is a minor peptide component of the insoluble fibrillar core of the Alzheimer's disease (AD) neuritic plaque. NAC amyloid fibrils seed the polymerization of A beta 1-40, the major AD amyloid protein. NAC is derived from a 14 kDa precursor protein, designated NACP, a member of a highly conserved family of heat-stable brain-specific acidic proteins which have been suggested to be involved in synapse formation and/or stabilization. NACP has also been suggested to play a role in AD. We present herein a conformational analysis of human NACP. NACP has a much larger Stokes radius (34 A) but sedimented more slowly (s20,w = 1.7S) than globular proteins of similar molecular weight, indicating that the native protein is elongated. Circular dichroism (CD) and Fourier-transform infrared spectroscopy (FTIR) indicate the absence of significant amounts of secondary structure in NACP, while CD and ultraviolet spectroscopy suggest the lack of a hydrophobic core. The conformational properties of NACP were unchanged by boiling and were independent of concentration, pH, salt, and chemical denaturants. These features indicate that NACP exists as a mixture of rapidly equilibrating extended conformers and is representative of a class of "natively unfolded" proteins, many of which potentiate protein-protein interactions.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amino Acid Sequence
  • Amyloid / chemical synthesis
  • Amyloid / chemistry*
  • Amyloid / isolation & purification
  • Amyloid / metabolism
  • Circular Dichroism
  • Cloning, Molecular
  • Escherichia coli / genetics
  • Humans
  • Molecular Sequence Data
  • Molecular Weight
  • Nerve Tissue Proteins*
  • Protein Conformation
  • Protein Folding*
  • Protein Precursors / chemical synthesis
  • Protein Precursors / chemistry*
  • Protein Precursors / isolation & purification
  • Protein Precursors / metabolism
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Spectroscopy, Fourier Transform Infrared
  • Synucleins
  • Ultracentrifugation


  • Amyloid
  • Nerve Tissue Proteins
  • Protein Precursors
  • Recombinant Proteins
  • Synucleins