High-Resolution Model of the Microtubule We recently obtained the structure of the tubulin dimer

We recently obtained the structure of the tubulin dimer Eva Nogales,*†§ Michael Whittaker,‡ Ronald A. Milligan,‡ and Kenneth H. Downing* by electron crystallography of zinc-induced tubulin sheets (Nogales et al., 1998a). Each tubulin monomer *Lawrence Berkeley National Laboratory Berkeley, California 94720 (Figure 1A) is a compact ellipsoid of approximate dimensions 46 3 40 3 65 Å (width, height, and depth, respec†Molecular and Cell Biology Department University of California at Berkeley tively) made up of three sequential domains: an N-terminal, nucleotide-binding domain; a smaller second Berkeley, California 94720 ‡Department of Cell Biology domain; and a predominantly helical C-terminal region. The a and b subunits are very similar, with the ab-dimer The Scripps Research Institute La Jolla, California 92037 being 46 3 80 3 65 Å. We have also calculated a 20 Å resolution three-dimensional (3D) map of the microtubule by cryoelectron microscopy and helical reconstruction and established the map polarity by comparison Summary with previous data (Sosa and Milligan, 1996; Sosa et al., 1997). The 3D map shows that the inside and outside A high-resolution model of the microtubule has been microtubule surfaces are very distinctive. The outside obtained by docking the crystal structure of tubulin surface is characterized by a shallow zigzag of density into a 20 Å map of the microtubule. The excellent fit that forms the crest of the protofilament. In a side view, indicates the similarity of the tubulin conformation in this surface is fairly flat with very shallow undulations. both polymers and defines the orientation of the tuIn contrast, the inside surface is deeply corrugated, with bulin structure within the microtubule. Long C-termithe connections between protofilaments lying close to nal helices form the crest on the outside of the protofilthe inner surface. Here we have docked the crystal strucament, while long loops define the microtubule lumen. ture of tubulin into the 3D map of the microtubule to The exchangeable nucleotide in b-tubulin is exposed create a near atomic model of the microtubule. The at the plus end of the microtubule, while the proposed model shows the detailed architecture of the microtucatalytic residue in a-tubulin is exposed at the minus bule and provides insight into the molecular basis for end. Extensive longitudinal interfaces between monothe observed properties of microtubules. mers have polar and hydrophobic components. At the lateral contacts, a nucleotide-sensitive helix interacts with a loop that contributes to the binding site of taxol Results in b-tubulin.