Abstract
Multivalency, the presence of multiple interfaces for intermolecular interactions, underlies many biological phenomena, including receptor clustering and cytosolic condensation. One of its ultimate purposes is to increase binding affinity, but systematic analyses of its role in complex biological assemblies have been rare. Presence of multiple copies of the microtubule-binding NDC80 complex is an evolutionary conserved but poorly characterized feature of kinetochores, the points of attachment of chromosomes to spindle microtubules. To address its significance, we engineered modules allowing incremental addition of NDC80 complexes. The modules’ residence time on microtubules increased exponentially with the number of NDC80 complexes. While modules containing a single NDC80 complex were unable to track depolymerizing microtubules, modules with two or more complexes tracked depolymerizing microtubules and stiffened the connection with microtubules under force. Cargo-conjugated modules of divalent or trivalent NDC80 stalled and rescued microtubule depolymerization in a force-dependent manner. Thus, multivalent microtubule binding through NDC80 clustering is crucial for force-induced modulation of kinetochore-microtubule attachments.
