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Cu(II) organizes β‐2‐microglobulin oligomers but is released upon amyloid formation
Author(s) -
Antwi Kwasi,
Mahar Maura,
Srikanth Rapole,
Olbris Mark R.,
Tyson Julian F.,
Vachet Richard W.
Publication year - 2008
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.073249008
Subject(s) - tetramer , chemistry , dimer , fibril , amyloid (mycology) , beta 2 microglobulin , biophysics , dynamic light scattering , amyloid fibril , crystallography , size exclusion chromatography , biochemistry , amyloid β , enzyme , materials science , biology , organic chemistry , nanotechnology , medicine , inorganic chemistry , disease , pathology , nanoparticle , immunology
β‐2‐Microglobulin (β2m) is deposited as amyloid fibrils in the bones and joints of patients undergoing long‐term dialysis treatment as a result of kidney failure. Previous work has shown that biologically relevant amounts of Cu(II) can cause β2m to be converted to amyloid fibrils under physiological conditions in vitro. In this work, dynamic light scattering, mass spectrometry, and size‐exclusion chromatography are used to characterize the role that Cu plays in the formation of oligomeric intermediates that precede fibril formation. Cu(II) is found to be necessary for the stability of the dimer and an initial form of the tetramer. The initially formed tetramer then undergoes a structural change to a state that no longer binds Cu(II) before progressing to a hexameric state. Based on these results, we propose that the lag phase associated with β2m fibril formation is partially accounted for by the structural transition of the tetramer that results in Cu(II) loss. Consistent with this observation is the determination that the mature β2m amyloid fibrils do not contain Cu. Thus, Cu(II) appears to play a catalytic role by enabling the organization of the necessary oligomeric intermediates that precede β2m amyloid formation.