The αβ tubulin heterodimer is the structural subunit of microtubules, which are cytoskeletal elements that are essential for intracellular transport and cell division in all eukaryotes. Each tubulin monomer binds a guanine nucleotide, which is non-exchangeable when it is bound in the α subunit, or N site, and exchangeable when bound in the β subunit, or E site. The α- and β-tubulins share 40% amino-acid sequence identity, both exist in several isotype forms, and both undergo a variety of post-translational modifications1. Limited sequence homology has been found with the proteins FtsZ2 and Misato3, which are involved in cell division in bacteria and Drosophila, respectively. Here we present an atomic model of the αβ tubulin dimer fitted to a 3.7-Å density map obtained by electron crystallography of zinc-induced tubulin sheets. The structures of α- and β-tubulin are basically identical: each monomer is formed by a core of two β-sheets surrounded by α-helices. The monomer structure is very compact, but can be divided into three functional domains: the amino-terminal domain containing the nucleotide-binding region, an intermediate domain containing the Taxol-binding site, and the carboxy-terminal domain, which probably constitutes the binding surface for motor proteins.
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We thank R. F. Ludueña for isotypically purified αβII and αβIII tubulin, M. Le for help with electron diffraction processing, and R. M. Glaeser and Y. L. Han for comments on the manuscript. Taxol was provided by the Drug Synthesis and Chemistry Branch, Division of Cancer Treatment of the National Cancer Institute. This work was supported by the NIH.
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Nogales, E., Wolf, S. & Downing, K. Structure of the αβ tubulin dimer by electron crystallography. Nature 391, 199–203 (1998). https://doi.org/10.1038/34465
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