Elucidating the mechanism of familial amyloidosis- Finnish type: NMR studies of human gelsolin domain 2.

ABSTRACT: Familial amyloidosis-Finnish type (FAF) results from a single mutation at residue 187 (D187N or D187Y) within domain 2 of the actin-regulating protein gelsolin. The mutation somehow allows a masked cleavage site to be exposed, leading to the first step in the formation of an amyloidogenic fragment. We have performed NMR experiments investigating structural and dynamic changes between wild-type (WT) and D187N gelsolin domain 2 (D2). On mutation, no significant structural or dynamic changes occur at or near the cleavage site. Areas in conformational exchange are observed between beta-strand 4 and alpha-helix 1 and within the loop region following beta-strand 5. Chemical shift differences are noted along the face of alpha-helix 1 that packs onto the beta-sheet, suggesting an altered conformat

SUBMITTER: Kazmirski SL 

PROVIDER: S-EPMC27087 | biostudies-literature | 2000 Sep

REPOSITORIES: biostudies-literature