A Unifying Hypothesis for the Conformational Change of Tubulin

Microtubule dynamic instability arises from the hydrolysis of GTP bound to the β-monomer of the tubulin dimer. The conformational change induced by hydrolysis is unknown, but microtubules disassemble into protofilaments of GDP-bound tubulin that curve away from the microtubule axis. This paper presents the unfolding of a portion of the tubulin molecule into the microtubule interior as a plausible, unifying explanation for diverse structural and kinetic features of microtubules. This is the first specific structural hypothesis for the hydrolysis induced conformational change of tubulin that simultaneously explains weakening of lateral bonds, bending about longitudinal bonds, changes in protofilament supertwist associated with GTP hydrolysis, structural features of GDP-tubulin double rings, faster disassembly at higher temperatures and slower disassembly in the presence of glycerol and deuterium oxide. As such, the hypothesis makes a strong case for further theoretical investigation and direct experimental tests.