Taken from Protein Structure & Function 2nd ed., C. Branden & J. Tooze, c 1999.
One subunit of Transthyretin.
Amyloid is a disfunction in which normally globular, soluble proteins polymerize & form insoluble aggregates of fibriles or plaques.
Amyloid fibriles are long, straight unbranched rods about 100 angstroms in diameter.
Using the protein transthyretin, Colin Blake and Louise Serpell (Oxford University) proposed a model for the structure of amyloid. By studying patients suffering familial amyloidotic polyneuropathy, they ascertained that a single point mutation (Val -> Met) in transthyritin causes the soluble, globular protein to polymerize and eventually deposit fibriles in the heart or eye. Transthyritin was shown to have a homotetramer structure, with its subunits folded in antiparallel beta structure.
It is thought that the C&D beta strands of transthyretin unfold to form the amyloid. Blake and Serpell's data indicate that a repeating pattern exists along the fiber axis, with structural repeats approximately every 115.5 angstroms. As seen above, the beta sheets in a globular protein are twisted and not planar, thus Blake and Serpell suggested that the repeats were due to a twisted beta sheet completing one full 360 degree turn every 115.5 angstroms. This can be visualized as below. Each color represents a protofilament composed of three pairs of antiparallel beta strands. A hydrophobic core exists between each each sheet, stabilizing the structure. The beta helix composes the core of the protofilament, and other material (i.e. polypeptide chain loops) surround this core.
