Intrinsic Bending of Microtubule Protofilaments

Department of Chemistry, James Franck Institute, and Computation Institute, University of Chicago, 5735 S. Ellis Avenue, Chicago, IL 60637, USA.
Structure (Impact Factor: 5.62). 03/2011; 19(3):409-17. DOI: 10.1016/j.str.2010.12.020
Source: PubMed


The complex polymerization dynamics of the microtubule (MT) plus end are closely linked to the hydrolysis of the GTP nucleotide bound to the β-tubulin. The destabilization is thought to be associated with the conformational change of the tubulin dimers from the straight conformation in the MT lattice to a curved conformation. It remains under debate whether this transformation is directly related to the nucleotide state, or a consequence of the longitudinal or lateral contacts in the MT lattice. Here, we present large-scale atomistic simulations of short tubulin protofilaments with both nucleotide states, starting from both extreme conformations. Our simulations indicate that both interdimer and intradimer contacts in both GDP and GTP-bound tubulin dimers and protofilaments in solution bend. There are no observable differences between the mesoscopic properties of the contacts in GTP and GDP-bound tubulin or the intradime and interdimer interfaces.

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    • "The allosteric model postulates that GDP favors curved dimers and PFs, whereas GTP favors straighter conformations (Nogales and Wang, 2006b; Wang and Nogales, 2005). However , this model is contested by the results of several experimental (Barbier et al., 2010; Buey et al., 2006; Nawrotek et al., 2011; Rice et al., 2008) and in silico (Gebremichael et al., 2008; Grafmü ller and Voth, 2011) studies. Those studies seem to support the lattice model, which posits that dimer conformational straightening occurs only upon recruitment into the growing MT lattice (Rice et al., 2008). "
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