Which component of microtubules is responsible for its dynamic instability?
Microtubule dynamic instability reflects differential nucleotide state of tubulin subunits within polymer lattice storing strain energy. Each heterodimer contains alpha tubulin with nonexchangeable GTP permanently trapped at N site maintaining structural integrity and longitudinal interface and beta tubulin with exchangeable E site that binds GTP in soluble pool. Upon incorporation at growing plus end beta GTP forms GTP cap of one to three dimer layers that prefers straight protofilament conformation and strong lateral bonds mediated by M loop. Soon after incorporation beta GTP hydrolyzed to GDP via catalytic glutamate contributed by adjacent alpha tubulin converting lattice to GDP bound state that favors curved conformation with stored elastic strain. Alpha GTP never hydrolyzes beta does not bind ATP. Therefore GTP bound beta tubulin confers stability its hydrolysis introduces vulnerability. Loss of cap exposes GDP lattice protofilaments peel outward causing catastrophe. This mechanism distinguishes microtubules from nucleotide independent intermediate filaments and explains polymerization force generation.
Ref: Alberts et al., Molecular Biology of the Cell 7th ed., Chapter 14: GTP beta tubulin role in dynamic instability cap model.