Binding Site Maturation Modulated by Molecular Density Underlies Ndc80 Binding to Kinetochore Receptor CENP-T.

ABSTRACT: Macromolecular assembly depends on tightly regulated pairwise binding interactions that are selectively favored at assembly sites while being disfavored in the soluble phase. This selective control can arise due to molecular density-enhanced binding, as recently found for the kinetochore scaffold protein CENP-T. When clustered, CENP-T recruits markedly more Ndc80 complexes than its monomeric counterpart, but the underlying molecular basis remains elusive. Here, we use quantitative in vitro assays to reveal two distinct mechanisms driving this behavior. First, Ndc80 binding to CENP-T is a two-step process: initially, Ndc80 molecules rapidly associate and dissociate from disordered N-terminal binding sites on CENP-T. Over time, these sites undergo maturation, resulting in stronger Ndc

SUBMITTER: Tarasovetc EV 

PROVIDER: S-EPMC10925139 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature