Identification of regions in apomyoglobin which form intermolecular interactions in amyloid aggregates using high-performance mass spectrometry
T13N4
N.S. Katina, M.Yu. Suvorina, E.I. Grigorashvili, V.V. Marchenkov, N.A. Ryabova, A.D. Nikulin,
A.K. Surin
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 as well as structural characteristics of amyloids are complicated because of heterogeneity and high molecular weight of the aggregates. We have used limited proteolysis and mass spectrometry for identification of regions in the polypeptide chain of apomyoglobin which give rise to intermolecular interactions in amyloid structures. The methods of tandem mass spectroscopy have allowed us to identify regions in the polypeptide chain of myoglobin which form the core of amyloid structures. It is shown that the main structural elements for the formation of the core of amyloid fibrils in myoglobin are regions from amino acid region 60 through 90 and from 97 through 124. These areas coincide well with the theoreticall prediction. The approach has made it possible to obtain important data on the structure of protein molecules in aggregates and on conformational rearrangements of apomyoglobin upon amyloid formation.
