Fibrillation and amyloid proteins

Connective tissues, collagen and hydrogels of nuclear pore proteins 

The failure of proteins to fold into their functional forms can occasionally lead to misfolding or conformational diseases.140 Many of these diseases are associated with the formation of amyloid protein, an insoluble material that is deposited as fibrils or plaques in different tissues and organs of the body. They include amyloid Ap protein as the major constituent of the plaques in Alzheimer patients, PrPc associated with neuro-degenerative diseases, a-synuclein (AS) associated with Parkinson s diseases, transthyretin (TTR) as a homotetrameric protein that is involved in the transport of thyroid hormones and retinol in human serum. In particular, the Ap protein is a peptide of 39-43 amino acids that is the 

The 140-residue protein AS is able to form amyloid fibrils and as such is the main component of protein inclusions involved in Parkinson s disease. Full-length 13C/15N-labelled AS fibrils and AS reverse-labelled for two of the most abundant amino acids, K and V, were examined by homonuclear and heteronuclear 2D and 3D NMR.147 Two different types of fibrils display chemical shift differences of up to 13 ppm in the l5N dimension and up to 5 ppm for the backbone and side-chain 13C chemical shifts. Selection of regions with different mobility indicates the existence of monomers in the sample and allows the identification of mobile segments of the protein within the fibril in the presence of monomeric protein. At least 35 C-terminal residues are mobile and lack a defined secondary structure, whereas the N terminus is rigid starting from residue 22. In addition, temperature-dependent sensitivity enhancement is also noted for the AS fibrils due to both the CP efficiency and motional interference with proton decoupling.148 

It appears that amyloid formation involves unordered or at least partly unfolded precursors. Thus, it is worthwhile to examine the fibrillation 

the components of hCT molecules observed by the DDMAS and CPMAS experiments are defined as A and B forms, respectively. For early stages, it is proposed163 that a formation of micelles corresponding to the a-helical bundle is reversibly formed from the monomers with the same aggregation number n0 (An0), 

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