Getting to the heart of beta-tubulin

Cellular microtubules assemble and disassemble at a variety of rates and frequencies, and these properties contribute directly to the cell-cycle-associated rearrangements of the microtubule cytoskeleton and to the molecular basis of mitosis. The kinetics of assembly/disassembly are governed, in part, by the hydrolysis of GTP bound to the beta-tubulin nucleotide-binding site. The beta-tubulin GTP-binding site, therefore, lies at the heart of microtubule assembly-disassembly kinetics, and the elucidation of its structure is central to an understanding of the cellular behaviour of microtubules. Unfortunately, the crystallographic structure of beta-tubulin is not yet available. In this review, we describe the progress being made using mutagenesis and biochemical studies to understand the structure of this unusual GTP-binding site.