Microtubule assembly governed by tubulin allosteric gain in flexibility and lattice induced fit

TY - JOUR

T1 - Microtubule assembly governed by tubulin allosteric gain in flexibility and lattice induced fit

AU - Igaev, Maxim

AU - Grubmüller, Helmut

N1 - Publisher Copyright: © Igaev and Grubmüller.

PY - 2018/4/13

Y1 - 2018/4/13

N2 - 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 αβ-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.

AB - 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 αβ-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.

UR - https://www.scopus.com/pages/publications/85051928561

U2 - 10.7554/eLife.34353

DO - 10.7554/eLife.34353

M3 - Article

C2 - 29652248

AN - SCOPUS:85051928561

SN - 2050-084X

VL - 7

JO - eLife

JF - eLife

M1 - e34353

ER -