Heparin acts as a structural component of β-endorphin amyloid fibrils rather than a simple aggregation promoter.
Royal Society of Chemistry
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Nespovitaya, N., Mahou, P., Laine, R., Schierle, G., & Kaminski, C. (2016). Heparin acts as a structural component of β-endorphin amyloid fibrils rather than a simple aggregation promoter.. Chemical Commununications, 53 1273-1276. https://doi.org/10.1039/c6cc09770g
The aggregation promoter heparin is commonly used to study the aggregation kinetics and biophysical properties of protein amyloids. However, the underlying mechanism for amyloid promotion by heparin remains poorly understood. In the case of the neuropeptide β-endorphin that can reversibly adopt a functional amyloid form in nature, aggregation in the presence of heparin leads to a loss of function. Applying correlative optical super-resolution microscopy methods, we show that heparin incorporates into emerging β-endorphin fibrils forming an integral component and is essential for amyloid templating. This will have direct implications on β-endorphin's normal physiological function and raises concerns on the biological relevance of heparin-promoted amyloid models.
This work was funded by grants from the Wellcome Trust, the Medical Research Council UK, the Alzheimer Research UK Trust, the Engineering and Physical Sciences Research Council UK, and the Biotechnology and Biological Sciences Research Council. NN was supported through Early PostDoc.Mobility personal fellowship from Swiss National Science Foundation.
External DOI: https://doi.org/10.1039/c6cc09770g
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263123