Making use of dynamic instability at the microtubule‐kinetochore interface

Abstract

The dynamic behavior of microtubules is essential for their functions. We have obtained the structure of two structural intermediates corresponding to the start and end points in the polymerization cycle that illustrate the conformational consequences of the nucleotide state and how they relate to longitudinal and lateral assembly. We propose that the polymorphism of assembly unique to tubulin reflects an exquisite tuning mechanism for the complex interaction of different microtubule intermediates with cellular factors that need to detect or make direct use of the growing or shortening state of microtubules to play functional roles at the right time and place in the cell. One such cellular component is the yeast Dam1 kinetochore complex. This complex self‐assembles around microtubules into rings and spiral‐like structures, but lacks the classical footprint on the microtubule lattice of motors and structural MAPs, allowing for its passive diffusion on the microtubule. When the microtubule depolymerizes the Dam1 ring uses the conformational strain of GDP tubulin within the lattice as tubulin relaxes into its curved state, to move processively, and without energy consumption of its own. A microtubule‐induced conformational change of the Dam1 complex ensures that ring formation does not precede engagement with a kinetochore microtubule.