Nicking and fragmentation are responsible for α‐lactalbumin amyloid fibril formation at acidic pH and elevated temperature

Rahamtullah; Rajesh Mishra

doi:10.1002/pro.4144

journal article Jun 17, 2021

Nicking and fragmentation are responsible for α‐lactalbumin amyloid fibril formation at acidic pH and elevated temperature

Rahamtullah Rajesh Mishra

Protein Science Vol. 30 No. 9 pp. 1919-1934 · Wiley

View at Publisher Save 10.1002/pro.4144

Abstract

AbstractAmyloid fibrils are ordered aggregates that may be formed from disordered, partially unfolded, and fragments of proteins and peptides. There are several diseases, which are due to the formation and deposition of insoluble β‐sheet protein aggregates in various tissue, collectively known as amyloidosis. Here, we have used bovine α‐lactalbumin as a model protein to understand the mechanism of amyloid fibril formation at pH 1.6 and 65°C under non‐reducing conditions. Amyloid fibril formation is confirmed by Thioflavin T fluorescence and atomic force microscopy (AFM). Our finding demonstrates that hydrolysis of peptide bonds occurs under these conditions, which results in nicking and fragmentation. The nicking and fragmentation have been confirmed on non‐reducing and reducing gel. We have identified the fragments by matrix‐assisted laser desorption ionization‐time of flight (MALDI‐TOF) mass spectrometry. The fragmentation may initiate nucleation as it coincides with AFM images. Conformational changes associated with monomer resulting in fibrillation are shown by circular dichroism and Raman spectroscopy. The current study highlights the importance of nicking and fragmentation in amyloid fibril formation, which may help understand the role of acidic pH and proteolysis under in vivo conditions in the initiation of amyloid fibril formation.

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Published: Jun 17, 2021
Vol/Issue: 30(9)
Pages: 1919-1934
License: View

Authors

R

Rahamtullah

School of Biotechnology Jawaharlal Nehru University New Delhi India

R

Rajesh Mishra

School of Biotechnology Jawaharlal Nehru University New Delhi India

Cite This Article

Rahamtullah, Rajesh Mishra (2021). Nicking and fragmentation are responsible for α‐lactalbumin amyloid fibril formation at acidic pH and elevated temperature. Protein Science, 30(9), 1919-1934. https://doi.org/10.1002/pro.4144

Nicking and fragmentation are responsible for α‐lactalbumin amyloid fibril formation at acidic pH and elevated temperature

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