Structural basis of tubulin recruitment and assembly by microtubule polymerases with tumor overexpressed gene (TOG) domain arrays
TOG (tumor overexpressed gene) domain arrays, found in microtubule polymerases such as yeast Alp14, organize and then polymerize αβ-tubulin at microtubule plus ends. Binding assays showed that TOG1 binds tubulin more strongly than TOG2, and a crystal structure of a Saccharomyces kluyveri Alp14 homodimer revealed two TOG1 and two TOG2 domains, each holding a tubulin dimer, arranged in a square with TOGs inside and tubulin outside. Combining crystallography with cryo-EM, the authors propose that this square “unfurls,” positioning tubulins into a protofilament-like assembly; in this state, the TOG2-bound α-tubulin shifts its T7 loop and H8 helix by about 5 and 10 Å to contact the TOG1-bound β-tubulin and its GDP nucleotide. The work supports a model in which TOG arrays act as molecular machines that recruit, pre-organize, and then add tubulin to the growing microtubule end, rather than simply delivering subunits one at a time.
