Title
Functionally Active Cross-Linked Protein Oligomers Formed by Homocysteine Thiolactone
Author
Kumari, Kritika, Gurumayum Suraj Sharma, Akshita Gupta, Khuraijam Surjalal Singh, and Laishram Rajendrakumar Singh
Year
2023
Journal
Scientific Reports
Abstract
Deposition of high-order protein oligomers is a common hallmark of a large number of human diseases and therefore, has been of immense medical interest. From the past several decades, efforts are being made to characterize protein oligomers and explore how they are linked with the disease pathologies. In general, oligomers are non-functional, rather cytotoxic in nature while the functional (non-cytotoxic) oligomers are quite rare. In the present study, we identified new protein oligomers of Ribonuclease-A and Lysozyme that contain functionally active fractions. These functional oligomers are disulfide cross-linked, native-like, and obtained as a result of the covalent modification of the proteins by the toxic metabolite, homocysteine thiolactone accumulated under hyperhomocysteinemia (a condition responsible for cardiovascular complications including atherosclerosis). These results have been obtained from the extensive analysis of the nature of oligomers, functional status, and structural integrity of the proteins using orthogonal techniques. The study implicates the existence of such oligomers as protein sinks that may sequester toxic homocysteines in humans.
Full Article
Instrument
J-810,V-660
Keywords
Functional (non-cytotoxic) oligomers