TBCE and TBCB in tubulin dimer dissociation

Microtubule (MT) depolymerisation dynamics are not well characterised. MTs comprise α-tubulin-β-tubulin heterodimers, and their dissociation is mediated by tubulin cofactors (TBCs). Here, Marina Serna and colleagues (p. 1824) use electron microscopy, image processing and X-ray diffraction to determine the 3D structure of the chaperone TBCE and the TBCE-TBCB-α-tubulin (αEB) complex that forms upon dimer dissociation, and describe its molecular architecture. They deduced that α-tubulin constitutes the central core of the complex and binds to the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain of TBCE through an EEY motif by performing peptide-binding studies. In combination with deletion-mutant analyses, the authors found that the TBCE CAP-Gly and leucine-rich repeat domains were important for destabilisation of the tubulin heterodimer. Using an in vitro assay, the authors then accurately measured the GTP:GDP ratio before and after tubulin dissociation. In contrast to polymerisation, the GTP:GDP ratio remained unchanged, indicating that dissociation of the stable tubulin heterodimer is energy independent. Therefore, the authors speculate that an unstable quaternary complex is formed upon the interaction of TBCE and TBCB with the α-tubulin-β-tubulin heterodimer, driving the formation of the αEB complex and MT depolymerisation.