Conformational flexibility of histone variant CENP-A^Cse4 is regulated by histone H4: A mechanism to stabilize soluble Cse4.

ABSTRACT: The histone variant CENP-A^Cse4 is a core component of the specialized nucleosome at the centromere in budding yeast and is required for genomic integrity. Accordingly, the levels of Cse4 in cells are tightly regulated, primarily by ubiquitin-mediated proteolysis. However, structural transitions in Cse4 that regulate its centromeric localization and interaction with regulatory components are poorly understood. Using time-resolved fluorescence, NMR, and molecular dynamics simulations, we show here that soluble Cse4 can exist in a "closed" conformation, inaccessible to various regulatory components. We further determined that binding of its obligate partner, histone H4, alters the interdomain interaction within Cse4, enabling an "open" state that is susceptible to proteolysis. This

SUBMITTER: Malik N 

PROVIDER: S-EPMC6311523 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature