Structural and functional analysis of cystatin E reveals enzymologically relevant dimer and amyloid fibril states.

ABSTRACT: Protein activity is often regulated by altering the oligomerization state. One mechanism of multimerization involves domain swapping, wherein proteins exchange parts of their structures and thereby form long-lived dimers or multimers. Domain swapping has been specifically observed in amyloidogenic proteins, for example the cystatin superfamily of cysteine protease inhibitors. Cystatins are twin-headed inhibitors, simultaneously targeting the lysosomal cathepsins and legumain, with important roles in cancer progression and Alzheimer's disease. Although cystatin E is the most potent legumain inhibitor identified so far, nothing is known about its propensity to oligomerize. In this study, we show that conformational destabilization of cystatin E leads to the formation of a domain-swapped dime

SUBMITTER: Dall E 

PROVIDER: S-EPMC6109925 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature