Title
Myoglobin forms amyloid fibrils by association of unfolded polypeptide segments
Author
Marcus Fa¨ndrich, Vincent Forge, Katrin Buder, Marlis Kittler, Christopher M. Dobson, Stephan Diekmann
Year
2003
Journal
PNAS
Abstract
Observations that beta-sheet proteins form amyloid fibrils under at least partially denaturing conditions has raised questions as to whether these fibrils assemble by docking of preformed -structure or by association of unfolded polypeptide segments. By using -helical protein apomyoglobin, we show that the ease of fibril assembly correlates with the extent of denaturation. By contrast, monomeric -sheet intermediates could not be observed under the conditions of fibril formation. These data suggest that amyloid fibril formation from apomyoglobin depends on disordered polypeptide segments and conditions that are selectively unfavorable to folding. However, it is inevitable that such conditions often stabilize protein folding intermediates.
Full Article
Instrument
J-720
Keywords
Circular dichroism, Secondary structure, Protein denaturation, Protein folding, Thermal stability, Thermodynamics, Biochemistry