Microtubule assembly governed by tubulin allosteric gain in flexibility and lattice induced fit.
Microtubules (MTs) are key components of the cytoskeleton and play a central role in cell division and development. MT assembly is known to be associated with a structural change in [Formula: see text]-tubulin dimers from kinked to straight conformations. How GTP binding renders individual dimers polymerization-competent, however, is still unclear. Here, we have characterized the conformational dynamics and energetics of unassembled tubulin using atomistic molecular dynamics and free energy calculations. Contrary to existing allosteric and lattice models, we find that GTP-tubulin favors a broad range of almost isoenergetic curvatures, whereas GDP-tubulin has a much lower bending flexibility. Moreover, irrespective of the bound nucleotide and curvature, two conformational states exist differing in location of the anchor point connecting the monomers that affects tubulin bending, with one state being strongly favored in solution. Our findings suggest a new combined model in which MTs incorporate and stabilize flexible GTP-dimers with a specific anchor point state.
['Igaev|Maxim|M|0000-0001-8781-1604', 'Grubmüller|Helmut|H|0000-0002-3270-3144']
D006153:Guanosine Diphosphate D006160:Guanosine Triphosphate D006801:Humans D008870:Microtubules D008958:Models, Molecular D056004:Molecular Dynamics Simulation D011487:Protein Conformation D055503:Protein Multimerization D013816:Thermodynamics D014404:Tubulin
microtubule tubulin molecular dynamics dynamic instability molecular biophysics none structural biology