As we know so far, around 25 proteins and peptides are known to involve in amyloid disease. If we assume that the fibrillation is an intrinsic feature of all polypeptides, and that we have tens thousand of proteins and peptides in body, why only a few of them convert to toxic aggregates and go to fibrillation process?
"If we assume that the fibrillation is an intrinsic feature of all polypeptides..."
Perhaps we shouldn't assume? Aggregation requires structural compatibility between constituent peptide chains, and such compatibility cannot happen too often between polypeptide sequences that have not evolved for such a purpose.
Perhaps - just my guess - fibrils are (not necessarily always) the result of the same molecular compatibility that is responsible for forming internal β-sheet structures in proteins. The necessary sequences are already there, and it's a matter of some misfolding (maybe a lack of some chaperone or a mutation that disfavors the "proper" fold) that allows these sequences to form intermolecular rather than intramolecular assemblies.
What is that compatibility, If see the list of amyloidogenic proteins/peptides https://doi.org/10.1146/annurev-biochem-
061516-045115
Many of them convert to fibril without having any mutation (sporadic).
On the other hand we have more that 150 disorders proteins but a few have potential to fibrillation and toxicity. Even there is no homology between hot spots part of these proteins, Is it?
Proc Natl Acad Sci U S A. 2002 Mar 5; 99(5): 2754–2759. doi: 10.1073/pnas.052706099PMCID: PMC122420PMID: 11880627Biophysics
Natural β-sheet proteins use negative design to avoid edge-to-edge aggregationArticle Richardson, J.S. & Richardson, D.C. Natural beta-sheet prote...
The above is quite informative, although it may not necessarily paint the whole picture.
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Biomolecules
- Peptides