The Determinants That Govern Microtubule Assembly from the Atomic Structure of GTP-Tubulin

Tubulin alternates between a soluble curved structure and a microtubule straight conformation. GTP binding to αβ-tubulin is required for microtubule assembly, but whether this triggers conversion into a straighter structure is still debated. This is due, at least in part, to the lack of structural data for GTP-tubulin before assembly. Here, we report atomic-resolution crystal structures of soluble tubulin in the GDP and GTP nucleotide states in a complex with a stathmin-like domain. The structures differ locally in the neighborhood of the nucleotide. A loop movement in GTP-bound tubulin favors its recruitment to the ends of growing microtubules and facilitates its curved-to-straight transition, but this conversion has not proceeded yet. The data therefore argue for the conformational change toward the straight structure occurring as microtubule-specific contacts are established. They also suggest a model for the way the tubulin structure is modified in relation to microtubule assembly.

Graphical AbstractFigure optionsDownload high-quality image (73 K)Download as PowerPoint slideHighlights
► The atomic-resolution structure of αβ-tubulin highlights the effect of the nucleotide.
► GTP/GDP exchange modifies the structure locally in the nucleotide site.
► The major change is a flipping of the nucleotide binding site T5 loop.
► Tubulin straightening occurs as microtubule-specific contacts are established.