Directed elongation model for microtubule GTP hydrolysis.
We propose a role for GTP hydrolysis in microtubule assembly in which the GTPase reaction serves to stabilize tubulin subunits in the microtubule. The GTPase reaction in tubulin subunits containing GTP at microtubule ends is presumed to occur predominately in subunits at one of the interfaces between a cap of GTP-containing tubulin subunit and a core of GDP-containing tubulin subunit in the microtubule, resulting in elongation of the core. The proposed model interprets the effects of GDP on microtubule assembly, using a reaction scheme in which GDP-containing tubulin subunits are able to add to microtubule ends. The model can account for the GTP requirement for microtubule assembly, the GDP inhibition of the rate for microtubule elongation, and the fact that a metastable state exists after the enzymic conversion of GTP to GDP, with microtubules which are at steady state. To account for the fact that the microtubule assembly and disassembly rates are nonlinearly dependent upon the tubulin subunit concentration and for the effects of GDP-containing tubulin subunits on the kinetic properties of microtubules, our scheme includes nonproductive as well as productive binding of GTP- and GDP-containing tubulin subunits. We compare our model with an alternative scheme [Hill, T. L. & Carlier, M. F. (1983) Proc. Natl. Acad. Sci. USA 80, 7234-7238], which interprets the effects of GDP on microtubule assembly using a reaction scheme in which GDP is able to exchange with GTP in GTP-containing tubulin subunits in the microtubule and in which the principal GTPase occurs in GTP-containing tubulin subunits at the microtubule/solution interface.
D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D013816:Thermodynamics; D014404:Tubulin / Q000378:metabolism*
D046911:Macromolecular Substances; D014404:Tubulin; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate