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Dynamic of β 2 ‐Microglobulin Fibril Formation and Reabsorption: The Role of Proteolysis
Author(s) -
Bellotti Vittorio,
Gallieni Maurizio,
Giorgetti Sofia,
Brancaccio Diego
Publication year - 2001
Publication title -
seminars in dialysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 78
eISSN - 1525-139X
pISSN - 0894-0959
DOI - 10.1046/j.1525-139x.2001.00030.x
Subject(s) - proteolysis , fibril , beta 2 microglobulin , amyloidosis , cleavage (geology) , protein folding , gene isoform , in vitro , beta (programming language) , medicine , pathogenesis , biochemistry , reabsorption , biophysics , chemistry , enzyme , pathology , biology , immunology , gene , paleontology , fracture (geology) , computer science , programming language , kidney
Dialysis‐related amyloidosis (DRA) is caused by the deposition, in target tissues, of β 2 ‐microglobulin (β 2 M) in fibrillar conformation. Several reports indicate that fibrillar β 2 M is chemically heterogeneous and such heterogeneity is partially related to the presence of truncated species of the protein. In association with the full‐length species, a β 2 M isoform lacking six N‐terminal residues is present in all the samples of our collection of ex vivo fibrils. The pattern of proteolytic cleavage in amyloidosis and in other diseases is completely different, as demonstrated by the absence in fibrillar β 2 M of the cleavage at lysine 58, which is contrary to that described in rheumatoid arthritis and other diseases. The role of limited proteolysis of β 2 M in the pathogenesis of the disease is uncertain. However, we have shown that the apparently minor modification of the intact protein, such as the removal of N‐terminal hexapeptide, is capable of dramatically affecting its stability, protection from proteolytic digestion, and enhance its capacity to make in vitro amyloid fibrils. The structure, folding dynamic, and function of the truncated species of β 2 M, peculiar of DRA, could shed new light on the mechanism of β 2 M fibril formation and reabsorption.