Microtubule structure and its stabilisation

Abstract

Microtubules are designed to be dynamically unstable. GTP hydrolysis converts an initially stable polymeric structure into an unstable one in which strain at the interfaces between longitudinal neighbours in the helical lattice of subunits is balanced by lateral interactions. However, stability can be modulated by a variety of factors, including associated proteins and a variety of drug molecules. Stabilising drugs such as Taxol and the assembly-promoting repeat motifs of tau protein occupy a special pocket in β-tubulin. Microtubule destabilising drugs such as colchicine alter the longitudinal interfaces of the subunits so that they cannot assemble into a microtubule lattice. These mechanisms are discussed in terms of the atomic structure of the protein.