Microtubules (MTs) are cytosolic filaments vital for multiple cellular processes such as cell division, cellular morphology and cellular trafficking. At the molecular level, the dynamic instability (random growth and shrinkage) of the MT is driven by the phosphorylation state of GTP in the β subunit of the tubulin dimers at the MT end. Here, we use large-scale molecular dynamics (MD) simulations and normal mode analysis (NMA) to characterize the effect of a single GTP cap layer on tubulin octamers composed by two neighboring protofilaments (PFs) of PF-A and PF-B. We utilize recent high-resolution structures of dynamic MTs by Nogales et al. to simulate a GDP octamer with and without a single GTP cap layer: termed as a GDP octamer and a GTP cap octamer respectively. We analyze multiple replicas of long-time atomistic MD simulations (~0.3 μs simulation time) of both GDP and GTP cap octamers. We observe a single GTP cap layer induces structural differences in neighboring PFs. We find the PF-A has a gradual curvature, compared to the “kinked” PF-B, resulting in either curling or splaying between these PFs. Also, we find longitudinal contacts at the dimer interface are greater for the PF-B, compared to the PF-A. Next, we have constructed GDP octamer model with its C-terminal tails. We will examine the effect of varying salt concentrations of NaCl and MgCl2 on the organization of these tails and protofilament conformations. Furthermore, using NMA, we will calculate mechanical properties such as flexural rigidity, persistence length, and bending modulus of these octamer systems.

Effect of nucleotide state and salt concentration on the protofilament conformation of tubulin octamers

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.