  Microtubule dynamic instability arises from the hydrolysis of GTP bound to
the beta-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. The hypothesis suggests further theoretical investigations and
direct experimental tests.
