An Interactive Jmol Tutorial about Tubulin bound to Stathmin-like Domain (SLD)

In cells, microtubule dynamics is regulated by stabilizing and destabilizing factors. The dynamics of microtubules are linked to GTP/GDP cycle.Whereas proteins in both categories have been identified, their mechanism of action is rarely understood at the molecular level. This is due in part to the difficulties faced in structural approaches to obtain atomic models when tubulin is involved. Two strategies have been used. The first exploited the properties of tubulin sequestering proteins to produce homogeneous complexes whose crystal structure has been determined. Alternatively, tubulin assemblies have been analyzed using cutting edge transmission electron microscopy (TEM).

Phosphoproteins of the stathmin family interact with the alpha-beta tubulin heterodimer (tubulin) and hence interfere with microtubule dynamics. The structure of the complex of GDP-tubulin with the stathmin-like domain of the neural protein RB3 reveals a head-to-tail assembly of two tubulins with a 91-residue RB3 alpha helix in which each copy of an internal duplicated sequence interacts with a different tubulin. As a result of the relative orientations adopted by tubulins and by their alpha and beta subunits, the tubulin:RB3 complex forms a curved structure. The RB3 helix thus most likely prevents incorporation of tubulin into microtubules by holding it in an assembly with a curvature very similar to that of the depolymerization products of microtubules.

In Fig 1. below is an electronmicrograph of negatively stained tubulin-R4 complexes. Species comprising four tubulin heterodimers (left) predominate, whereas complexes with three tubulins are also identified (right). Their dimensions (
55 Å X 355 Å and 55 Å X 265 Å, respectively) are consistent with those of a smaller SLD complex comprising two tubulins (15). Scale bar, 100 Å. (Mignot I. et al, JBC 2012)

Fig 2. shows model resulting from the repetition of T4R4 showing that the relative orientations of the tubulin subunits in T4R4 are close to those in a ring.Each T4R4 is colored differently. The resulting flat helix is viewed along its axis (left) and nearly perpendicularly to it (right). (Mignot I. et al, JBC 2012)

Fig (1)                                                                      Fig (2)