Identification of Regions in Apomyoglobin that Form Intermolecular Interactions in Amyloid Aggregates Using High-Performance Mass Spectrometry

• Published in: Journal of analytical chemistry (New York, N.Y.) N.Y.), 2017-12, Vol.72 (13), p.1271-1279
• Main Authors: Katina, N. S., Suvorina, M. Yu, Grigorashvili, E. I., Marchenkov, V. V., Ryabova, N. A., Nikulin, A. D., Surin, A. K.
• Format: Article
• Language: English
• Subjects: Aggregates; Analytical Chemistry; Chains; Chemistry; Chemistry and Materials Science; Glycoproteins; Mass spectrometry; Molecular structure; Myoglobin; Myoglobins; Organs; Polypeptides; Proteins; Scientific imaging; Spectroscopy; Structural members; Structure
• ISSN: 1061-9348; 1608-3199
• DOI: 10.1134/S1061934817130056

The formation of amyloid aggregates in human organs and tissues causes the development of incurable diseases. However, experimental studies of the mechanism of amyloid formation by proteins and the structural characteristics of amyloids are complicated because of the heterogeneity and high molecular weight of the aggregates. We used limited proteolysis and mass spectrometry for the identification of regions in the apomyoglobin polypeptide chain, which give rise to intermolecular interactions in amyloid structures. Tandem mass spectroscopy enabled the identification of regions in the myoglobin polypeptide chain, which form the core of amyloid structures. It was shown that the main structural elements for the formation of the core of amyloid fibrils in myoglobin were regions from 60 through 90 and from 97 through 124 amino acid residues. These regions coincide well with those theoretically predicted. This approach yielded important data on the structure of protein molecules in aggregates and on conformational rearrangements of apomyoglobin upon amyloid formation.