ABSTRACT
αβ-tubulin heterodimers self-assemble to form microtubules nucleated by γ-tubulin in the cell. γ-tubulin is believed to recruit the αβ-tubulin dimers that form the minus ends of microtubules, but the molecular mechanism of this action remains a matter of heated controversy. Still less is known about the function and molecular interactions of δ-tubulin and ε-tubulin. δ-tubulin may seed the formation of the C triplet tubules in the basal bodies of Chlamydomonas and ε-tubulin is known to localize to the centrosome in a cell cycle-dependent manner. Using the structure of αβ tubulin as a model, we have analyzed the sequences of γ-, δ- and ε-tubulin in regions corresponding to different polymerization interfaces in the tubulin αβ dimer. The sequence comparisons sometimes show clear conservation, pointing to similar types of contacts being functionally important for the new tubulin considered. Conversely, certain surfaces show marked differences that rule out equivalent interactions for non-microtubular tubulins. This sequence/structure analysis has led us to structural models of how these special tubulins may be involved in protein-protein contacts that affect microtubule self-assembly. δ-tubulin most likely interacts longitudinally with α-tubulin at the minus ends of microtubules, while ε-tubulin most likely binds to the plus end of β-tubulin. Conservation of key residues in γ-tubulin suggests that it is capable of longitudinal self-assembly. The implications for the protofilament and template models of nucleation are considered.
