Estimates of lateral and longitudinal bond energies within the microtubule lattice

AUTOR(ES)
FONTE

The National Academy of Sciences

RESUMO

We developed a stochastic model of microtubule (MT) assembly dynamics that estimates tubulin–tubulin bond energies, mechanical energy stored in the lattice dimers, and the size of the tubulin-GTP cap at MT tips. First, a simple assembly/disassembly state model was used to screen possible combinations of lateral bond energy (ΔGLat) and longitudinal bond energy (ΔGLong) plus the free energy of immobilizing a dimer in the MT lattice (ΔGS) for rates of MT growth and shortening measured experimentally. This analysis predicts ΔGLat in the range of −3.2 to −5.7 kBT and ΔGLong plus ΔGS in the range of −6.8 to −9.4 kBT. Based on these estimates, the energy of conformational stress for a single tubulin-GDP dimer in the lattice is 2.1–2.5 kBT. Second, we studied how tubulin-GTP cap size fluctuates with different hydrolysis rules and show that a mechanism of directly coupling subunit addition to hydrolysis fails to support MT growth, whereas a finite hydrolysis rate allows growth. By adding rules to mimic the mechanical constraints present at the MT tip, the model generates tubulin-GTP caps similar in size to experimental estimates. Finally, by combining assembly/disassembly and cap dynamics, we generate MT dynamic instability with rates and transition frequencies similar to those measured experimentally. Our model serves as a platform to examine GTP-cap dynamics and allows predictions of how MT-associated proteins and other effectors alter the energetics of MT assembly.

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