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Variant plasma gelsolin responsible for familial amyloidosis (Finnish type) has defective actin severing activity
Author(s) -
Weeds A.G.,
Gooch John,
McLaughlin P.,
Maury C.P.J.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80452-z
Subject(s) - gelsolin , proteolysis , mutant , amyloidosis , actin , mutation , mutant protein , chemistry , wild type , microbiology and biotechnology , actin binding protein , asparagine , biochemistry , biology , amino acid , actin cytoskeleton , cytoskeleton , medicine , pathology , gene , cell , enzyme
Familial amyloidosis, Finnish type is caused by a single base mutation in gelsolin, an actin filament severing and capping protein that is present in most tissues and in blood plasma. The mutation replaces aspartic acid with asparagine at residue 187 of the plasma sequence. This renders the gelsolin susceptible to proteolysis as a consequence of which amyloid protein is formed. Here it is shown that the mutant protein in plasma from a patient homozygous for this mutation lacks both actin severing and nucleating activities. Evidence is presented that the cleaved mutant gelsolin has dissociated under non‐denaturing conditions and that the resultant 65,000 and 55,000 M r C‐terminal fragments aggregate.