NR AOGI
AU Johansson,J.
TI Molecular determinants for amyloid fibril formation: lessons from lung surfactant protein C.
QU Swiss Medical Weekly : official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 2003 May 17; 133(19-20): 275-82
PT journal article; review; review, tutorial
AB Amyloid fibrils are polymers composed of proteins in beta-sheet conformation, which are found in at least 20 diseases for which no cure is available. These diseases include Alzheimer's disease and spongiform encephalopathies, in which the amyloid beta-peptide and the prion protein (PrP), respectively, form amyloid. All fibrils are morphologically very similar although the native structures of the corresponding proteins are widely different. Proteins that are not known to form fibrils in vivo can do so under conditions where unfolding intermediates are well populated. This indicates that fibril formation can arise from most, if not all, polypeptide chains under certain conditions, and that nature has found ways to avoid fibrillogenic protein conformations. In support of this, it was recently found that unpaired beta-strands present in native proteins are prevented from forming intermolecular beta-sheets, by strategic placement of prolines and charged residues for example. Structural studies of the lung surfactant-associated protein C (SP-C) have revealed determinants for amyloid fibril formation. The poly-valine alpha-helix of SP-C spontaneously converts to beta-sheet aggregates in vitro and SP-C amyloid fibrils are found in pulmonary alveolar proteinosis. A beta, PrP, and SP-C harbour an alpha-helix which is strongly predicted to form a beta-strand, and in all cases investigated so far such alpha-helix/beta-sheet discordance correlates with the ability to form beta-sheet aggregates and fibrils.
ZR 89
MH Alzheimer Disease/metabolism; Amino Acid Sequence; Amyloid beta-Protein/biosynthesis/*chemistry; Human; Models, Molecular; Molecular Sequence Data; Peptides/chemistry; Prion Diseases/metabolism; *Protein Conformation; Protein Folding; Protein Structure, Secondary; Pulmonary Surfactants/*chemistry; Support, Non-U.S. Gov't
AD Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, Uppsala, Sweden. jan.johansson@vmk.slu.se
SP englisch
PO Schweiz