Proteolytic generation and aggregation of peptides from transmembrane regions: lung surfactant protein C and amyloid beta-peptide

Cell Mol Life Sci. 2004 Feb;61(3):326-35. doi: 10.1007/s00018-003-3274-6.

Abstract

The formation of amyloid fibrils is associated with several devastating diseases in humans and animals, including e.g. Alzheimer's disease (AD) and the spongiform encephalopathies. Here, we review and discuss the current knowledge on two amyloid peptides: lung surfactant protein C (SP-C) and the amyloid beta-peptide (Abeta), implicated in human lung disease and in AD, respectively. Both these hydrophobic peptides are derived from the transmembrane region of their precursor protein, and can transit from a monomeric alpha-helical state to a beta-sheet fibril. The alpha helices of SP-C and Abeta are composed of amino acid residues with inherently higher propensities for beta strand than helix conformation. Their helical states are stabilized by a membrane environment, and loss of membrane association thus promotes structural conversion and fibril formation. We speculate that the loss of structural context for sequences with a high propensity for formation of beta sheets may be a common feature of amyloid formation in general.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Humans
  • Neurofibrils / metabolism
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism*
  • Protein Conformation
  • Pulmonary Surfactant-Associated Protein C

Substances

  • Amyloid beta-Peptides
  • Peptides
  • Pulmonary Surfactant-Associated Protein C
  • SFTPC protein, human