Binding site maturation modulated by molecular density underlies Ndc80 binding to kinetochore receptor CENP- T

• 成果类型: Article
• 署名作者: Tarasovetc, Ekaterina, V; Sissoko, Gunter B.; Maiorov, Aleksandr; Mukhina, Anna S.; Ataullakhanov, Fazoil I.; Cheeseman, Iain M.; Grishchuk, Ekaterina L.
• 署名单位: University of Pennsylvania; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11090
• DOI: 10.1073/pnas.2401344121
• 发表日期: 2024-12-24
• 关键词: aurora-b kinase; mechanisms; centromere; complex; inner; phosphorylation; localizes; platform

摘要

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, 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 that this maturation transition is regulated by a kinetic barrier that is sensitive to the molecular environment. In the soluble phase, binding site maturation is slow, but sensitivities, which correlate with their different amino acid content and predicted binding conformations. This clustering- induced maturation is evident in dividing human cells, suggesting a distinct regulatory entry point for controlling kinetochore molecular crowding may represent a general mechanism for promoting the formation of macromolecular structures.