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

submitted on 20.01.2021, 15:39 and posted on 21.01.2021, 12:05 by Bharti Koshti, Ramesh, Singh, Vivekshinh Kshtriya, Shanka Walia, Dhiraj Bhatia, khashti Ballabh Joshi, Nidhi Gour

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.




Email Address of Submitting Author


Indrashil University



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest to declare

Version Notes

This is the first preliminary draft. More data will be added in subsequent version