Unwinding fibril formation of medin, the peptide of the most common form of human amyloid.
Medin amyloid affects the medial layer of the thoracic aorta of most people above 50 years of age. The consequences of this amyloid are not completely known but the deposits may contribute to diseases such as thoracic aortic aneurysm and dissection or to the general diminished elasticity of blood vessels seen in elderly people. We show that the 50-amino acid residue peptide medin forms amyloid-like fibrils in vitro. With the use of Congo red staining, Thioflavin T fluorescence, electron microscopy, and a solid-phase binding assay on different synthetic peptides, we identified the last 18-19 amino acid residues to constitute the amyloid-promoting region of medin. We also demonstrate that the two C-terminal phenylalanines, previously suggested to be of importance for amyloid formation, are not required for medin amyloid formation.
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.
Annika
A
Larsson
Linda
L
Söderberg
Gunilla T
GT
Westermark
Knut
K
Sletten
Ulla
U
Engström
Lars O
LO
Tjernberg
Jan
J
Näslund
Per
P
Westermark
D000465:Algorithms; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D000954:Antigens, Surface / Q000737:chemistry*; D006801:Humans; D008894:Milk Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry
D000682:Amyloid; D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008894:Milk Proteins; D010455:Peptides