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Nucleotide-dependent lateral and longitudinal interactions in microtubules
Andrea Grafmüller1, Eva G Noya, Gregory A Voth
1Theory and Biosystems, Max Planck Institute for Colloids and Interfaces, 14424 Potsdam, Germany. andrea.grafmueller@mpikg.de
Journal of Molecular Biology
|April 2, 2013
Summary
Microtubule stability is influenced by guanosine triphosphate nucleotide (NT) state. Simulations reveal NT-induced changes in protein loops and bonds, affecting microtubule lattice contacts.
Area of Science:
- Biophysics
- Structural Biology
- Molecular Dynamics
Background:
- Microtubule (MT) stability is intrinsically linked to the nucleotide-binding state of β-tubulin, specifically the hydrolysis of guanosine triphosphate (GTP).
- The precise molecular mechanisms by which the nucleotide state modulates the stability of inter-tubulin contacts within the MT lattice remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanism connecting the nucleotide-binding state to microtubule lattice contact stability.
- To investigate how nucleotide hydrolysis influences tubulin conformation and inter-tubulin interactions.
Main Methods:
- Large-scale atomistic molecular dynamics simulations of various tubulin aggregates (dimers, protofilaments, lattice patches).
- Coarse-grained (CG) analysis of simulated fluctuations to assess bond stability and structural changes.
- Examination of tubulin structures in both nucleotide-bound states (GTP and GDP).
Main Results:
- Simulations identified specific protein regions sensitive to the nucleotide state and inter-tubulin contacts.
- Coarse-grained analysis indicated how structural alterations impact protein-protein bonds.
- Results suggest the nucleotide state induces changes in the H1-S2 loop and strengthens longitudinal bonds.
Conclusions:
- The nucleotide state significantly impacts microtubule structure by altering key loop conformations and inter-tubulin bond stability.
- These nucleotide-induced structural changes favor the formation of stable lateral contacts within the microtubule lattice.
- A potential molecular mechanism for nucleotide-dependent microtubule stabilization is proposed, involving the H1-S2 loop and M-loop positioning.
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