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Schlagwörter:
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Zusammenfassung:
Microtubules (MTs), mesoscopic cellular filaments, grow primarily by the addition
of GTP-bound tubulin dimers at their dynamic flaring plus-end tips. They operate
as chemomechanical energy transducers with stochastic transitions to an astounding
shortening motion upon hydrolyzing GTP to GDP. Time-resolved dynamics of the
MT tip—a key determinant of this behavior—as a function of nucleotide state, internal
lattice strain, and stabilizing lateral interactions have not been fully understood. Here
we use atomistic simulations to study the spontaneous relaxation of complete GTP-MT
and GDP-MT tip models from unfavorable straight to relaxed splayed conformations
and to comprehensively characterize the elasticity of MT tips. Our simulations reveal
the dominance of viscoelastic dynamics of MT protofilaments during the relaxation
process, driven by the stored bending-torsional strain and counterbalanced by the
interprotofilament interactions. We show that the posthydrolysis MT tip is exposed
to higher activation energy barriers for straight lattice formation, which translates into
its inability to elongate. Our study provides an information-driven Brownian ratchet
mechanism for the elastic energy conversion and release by MT tips and offers insights
into the mechanoenzymatics of MTs.
