Amyloid like Aggregates Formed by the Self-Assembly of Proline and Hydroxyproline

Abstract

<p>Single amino acid based self-assembled structures have gained a lot of interest recently owing to their pathological significance in metabolite disorders. There is plethora of significant research work which illustrate amyloid like characteristics of assemblies formed by aggregation of single amino acids like Phenylalanine, Tyrosine, Tryptophan, Cysteine and Methionine and its implications in pathophysiology of single amino acid metabolic disorders like phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria and hypermethioninemia respectively. Hence, studying aggregation behaviour of single amino acids is very crucial to assess the underlying molecular mechanism behind metabolic disorders. In this manuscript we report for the very first time the aggregation properties of non-aromatic single amino acids Hydroxy-proline and Proline. The morphologies of these were studied extensively by Optical microscopy (OM), ThT binding fluorescence microscopy, Scanning Electron Microscopy (SEM) and Atomic force microscopy (AFM). It can be assessed that these amino acids form globular structures at lower concentrations and gradually changes to tape like structures on increasing the concentration as assessed by AFM. ThT and CR binding assay reveal the aggregates do have amyloid like characteristics. Further MTT assays on SHSY5Y neural cell lines reveal cytotoxicity and the aggregates caused significant cell death in dose dependent manner. These results have important implications in understanding the pathophysiology of single amino acid disorders like Hyperprolinemia and Hydroxyprolinemia in association with amyloid diseases. The symptoms of these diseases are also accompanied by extensive neurological problems like intellectual disability, seizures and psychiatric problems which further evince amyloid like etiology for these rare in-born errors of metabolism.</p>

Interactions between Lipid Vesicle Membranes and Single Amino Acid Fibrils: Probable Origin of Specific Neurological Disorders

“…However, very recently, some nonaromatic amino acids have been reported to form similar fibrillar aggregates to that of aromatic amino acids. 9,16 For example, the nonaromatic amino acids, like methionine (Met), cysteine (Cys), proline (Pro), hydroxyproline (Hyp), etc. also form amyloid-like fibrillar deposition which is cytotoxic to cells.…”

Aggregation characteristics of non-aromatic polar amino acids and its association to amyloids

“…Recently we also reported unusual aggregates formed by proline, hydroxyproline, and lysine which also revealed cytotoxicity to ShS5Y neural cell lines as confirmed by MTT assays. 11 Hence, motivated by the previous research studies and our own investigation on single amino acid self-assembly and its implications in diseases, we were motivated to study the aggregation properties of other non-aromatic amino acids (Gln, Ser, Thr, Ala, Asn, Arg, Asp, Glu) and one aromatic acid (His) extensively under varying concentration and ageing time. The excess of these amino acids in body causes disease conditions like hyperserinemia, 12 histidinemia 13 and threoninemia.…”

Controlled self-assembly of modified aromatic amino acids

“…4 In the past few decades, there has been a considerable amount of research which is pursued in single amino acids and modified single amino acids. [5][6][7][8][9][10][11][12] In this context, Gazit et al reported amyloid-like structure formed by phenylalanine, 5 tyrosine 6 , and tryptophan. 7 Sarkar et al reported the fibrillar structure of glycine.…”

“…13 Wangoo and co-workers demonstrated the self-assembly of aromatic single amino acids, [14][15][16] and studied them extensively via various biophysical assays such as FTIR, NMR, TGA, and XRD. 8,9,13,14 Scheme 1: Chemical structure of Z-Phe-OH, Z-Trp-OH, Z-Tyr-OH, and Fmoc-Tyr(tbu)-OH.…”

“…Since our group has been working on the molecular self-assembly and assessing the selfassembly of the single amino acids, 8,9,17,18 modified single amino acids, 19 peptides, [20][21][22][23][24][25][26] nanoparticle/nanomaterial, [27][28][29] and heterocyclic [30][31][32][33][34][35] compounds. Our group reported for the very first time the amyloid-like self-assembled structure formed by the non-aromatic single amino acid cysteine and methionine 8 . Recently our group has also reported the amyloid-like structure formed by proline and hydroxyproline.…”