   3.6.5.6 | more |
GTP binding to the alpha occurs in the dimerization region between the alpha and beta monomers and remains unhydrolyzed. This is called the non-exchangeable site or N-site. GTP binding to beta-tubulin sits at the interface between two dimers within the protofilament, the longitudinal lattice of tubulin dimers running parallel to the microtubule filament long axis. Tubulin controls microtubule dynamics, analysis of GTP hydrolysis on reconstructed microtubules, mechanism, overview. GTP binding to the beta tubulin is hydrolyzable and this site is called the exchangeable site or E-site. Hydrolysis of GTP at the E-site is required for microtubule dynamic instability. GTP hydrolysis leads to the compaction of the lattice around the interdimer longitudinal interface sandwiching the E-site nucleotide. This compaction in turn results in a conformational rearrangement in all alpha-tubulin monomers corresponding to a small rotation of the intermediate domain and C-terminal H11-H12 helices with respect to the N-terminal domain in alpha-tubulin. Additionally, helix H8 from alpha-tubulin is also distorted in the GDP-state. The hydrolysis is immediate, but the probability of hydrolysis within a certain time is increased when the next dimer binds. Such catalysis leads to a situation where dimers at the end of the filament typically have GTP, and are in a non-compacted, straight conformation. This is called the GTP cap. Dimers within the body of the filament are typically in the GDP-state and prefer to be in the compacted, bent conformation. Due to binding to neighbors, the GDP dimers cannot compact and are held straight. Thus, GDP dimers in the body are in a high potential energy state, spring-loaded to compact whenever constraints are relaxed. The purpose of the GTPase is to force dimers within the body into this spring-loaded state. When the dimers at the top are lost or hydrolyzed stochastically, the end cap loses coherence and the entire microtubule bends back to relax the dimers to their lowest energy state. The longitudinal binding is less affected by the hydrolysis and protofilaments peel back into rings unraveling the microtubule |
Homo sapiens |
? |
- |
- |
