Destabilization of Ca2+-free gelsolin may not be responsible for proteolysis in Familial Amyloidosis of Finnish Type.

ABSTRACT: Mutations at position 187 in secreted gelsolin enable aberrant proteolysis at the 172-173 and 243-244 amide bonds, affording the 71-residue amyloidogenic peptide deposited in Familial Amyloidosis of Finnish Type (FAF). Thermodynamic comparisons of two different domain 2 constructs were carried out to study possible effects of the mutations on proteolytic susceptibility. In the construct we consider to be most representative of domain 2 in the context of the full-length protein (134-266), the D187N FAF variant is slightly destabilized relative to wild type (WT) under the conditions of urea denaturation, but exhibits a T(m) identical to WT. The D187Y variant is less stable to intermediate urea concentrations and exhibits a T(m) that is estimated to be approximately 5 degrees C lower than WT

SUBMITTER: Ratnaswamy G 

PROVIDER: S-EPMC30139 | biostudies-literature | 2001 Feb

REPOSITORIES: biostudies-literature