Copyright (C) 1999, FUNPEP.
This part of the FUNPEP project is a bit different from all the others. The
peptides on these pages were not chosen because of some kind of sequence similarity,
what is more, they hardly have any. Their common, and very starnge property is the
ability to form amyloid plaques (or fibrils). The exact structure and the formation
of these supermolacular structures are still subject of research, but there are
lots of promising results.
As a part of the FUNPEP project, we made a small
collection of peptides, which are known to form these amyloid plaques. Sequences,
including respective animal analogues, were extracted from SWISSPROT, and aligned.
These sequences and some words about the peptides can be found under the links in the table below.
Some molecular modelling was also perfomed, to show some possible structures of
amyloids. The result of modelling is here.
The medical points of amyloidosis was not in our interest, if you want to find information about that, go here.
Amyloid plaque (or fibril) formation refers to an in vivo process in which one of the human amyloidogenic proteins abnormally self assembles into a fibril 60-100 angstrom in width and of a variable length; the fibril has a characteristic cross-beta repeat structure where the individual beta strands composing the fibril are oriented perpendicular to the long axis of the fibril. The amyloidogenic proteins exhibit little sequence or structural homology, yet they are able to make amyloid fibrils of similar structure, as discerned from fiber X-ray diffraction patterns, their morphology in electron micrographs, and their ability to bind certain dyes (e.g. Congo Red) and exhibit birefringence. More information about the structure of amyloid fibers can be found here, about the dye-binding property here.
Amyloidogenic diseases and proteins are reviewed by J.W. Kelly in Curr. Opin. Struct. Biol. 6, 11-17. (1996):
| CJD | spongiform encepalopathies | prion protein fragments |
|---|---|---|
| APP | Alzheimer | beta protein fragment 1-40/43 |
| HRA | hemodialysis-related amyloidosis | beta-2 microglobin* |
| PSA | primary systmatic amyloidosis | immunoglobulin light chain and fragments |
| SAA 1 | secondary systmatic amyloidosis | serum amyloid A 78 residue fragment |
| FAP I** | familial amyloid polyneuropathy I | transthyretin fragments, 50+ allels |
| FAP III | familial amyloid polyneuropathy III | apolipoprotein A-1 fragments |
| CAA | cerebral amyloid angiopathy | cystatin C minus 10 residues |
| FHSA | Finnish hereditary systemic amyloidosis | gelsolin 71 aa fragment |
| IAPP | type II diabetes | islet amyloid polypeptide fragment (amylin) |
| ILA | injection-localized amyloidosis | insulin |
| CAL | medullary thyroid carcinoma | calcitonin fragments |
| ANF | atrial amyloidosis | atrial natriuretic factor |
| NNSA | non-neuropathic systemic amylodosis | lysozyme and fragments |
| HRA | hereditary renal amyloidosis | fibrinogen fragments |
* homologous to immunoglobin, so a predicted paralogous disease.The huntingtin peptide of Huntington's disease also known as an amyloid-forming one. The main differece is that its aggregation is caused by a long repeat of glutamins. Because of this we left it out from our studies.
** also called senile systemic amyloidosis, prealbumin is synonymous with transthyretin.