Gelsolin pathogenic Gly167Arg mutation promotes domain-swap dimerization of the protein.

ABSTRACT: AGel amyloidosis is a genetic degenerative disease characterized by the deposition of insoluble gelsolin protein aggregates in different tissues. Until recently, this disease was associated with two mutations of a single residue (Asp187 to Asn/Tyr) in the second domain of the protein. The general opinion is that pathogenic variants are not per se amyloidogenic but rather that the mutations trigger an aberrant proteolytic cascade, which results in the production of aggregation prone fragments. Here, we report the crystal structure of the second domain of gelsolin carrying the recently identified Gly167Arg mutation. This mutant dimerizes through a three-dimensional domain swapping mechanism, forming a tight but flexible assembly, which retains the structural topology of the monomer. To date,

SUBMITTER: Boni F 

PROVIDER: S-EPMC5886171 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature