Microtubule growth and dynamics

Real-time 3-D modeling by interactive computer graphics offers an effective tool to understand and interpret complex structural scenarios involving, for example, the nucleation, growth and turnover of large supramolecular assemblies. As illustrated in Fig. 1, in the case of microtubules - protein filaments involved in cytoarchitecture, cell division and intracellular transport - their growth is nucleated from alpha/beta tubulin "rings" which unfold so as to become the polymer's "protofilaments" (Erickson and Stoffler, 1996).

Alpha and beta tubulin represent the main subunits of eukaryotic microtubules, gamma tubulin nucleates these microtubules and regulates their dynamics at the minus end, and FtsZ, a prokaryotic homologue of the tubulins that is the major cytoskeletal protein in bacterial cell division. Both alpha/beta tubulin and FtsZ assemble into straight protofilaments that can associate further to make 2-D protofilament sheets. The protofilament sheet of alpha/beta tubulin makes the microtubule wall. FtsZ protofilaments apparently form a contractile apparatus that powers bacterial cell division, but its structure is still unknown.

Here we suggest an alternative model for microtubule nucleation, consistent with the proposal that gamma tubulin rings are structural homologues of alpha/beta and FtsZ rings (Erickson and Stoffler, 1996). The new model is also consistent with earlier work on the homogeneous nucleation of microtubules, and provides a mechanism by which gamma tubulin can interact with beta, as suggested by genetics. We have used a 3-D drawing program to construct new models illustrating the structure of tubulin rings and microtubule nucleation (Fig. 1a-c).

Figure 1: Models of tubulin rings and the related spiral polymer. Subunits in the curved conformation are modeled with a 20-23 degree tilt at the upper interface forming the longitudinal bond. The 4 nm spacing is maintained along the outer circumference. For the alpha/beta ring, the alpha subunit is assumed to be in the straight conformation and the tilt is only applied to the beta subunit. For FtsZ and gamma tubulin all subunits are in the curved conformation. (b) The microtubule lattice and the relation of rings to protofilaments. Longitudinal bonds connect alternating alpha and beta subunits into protofilaments, and lateral bonds connect subunits into the 3-start helix, one of which is highlighted. The 3-start helix connects primarily alpha to alpha and beta to beta, but there is a discontinuity or seam where alpha connects to beta. (c) Nucleation of microtubule assembly by a gamma tubulin spiral. This spiral extends a short length of straight protofilament, which serves as a stable seed for nucleation of a second protofilament. Alpha/beta subunits form lateral bonds to the gamma tubulin protofilament, and longitudinal bonds to each other. When this second protofilament has achieved three consecutive alpha/beta subunits, growth is more favorable than disassembly and the microtubule should be nucleated.

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