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Mal3, the Schizosaccharomyces pombe homolog of EB1, changes the microtubule lattice

Nature Structural & Molecular Biology volume 15, pages 1102–1108 (2008)Cite this article

Abstract

In vitro studies of pure tubulin have suggested that tubulin heterodimers in cells assemble into B-lattice microtubules, where the 8-nm dimers in adjacent protofilaments are staggered by 0.9 nm. This arrangement requires the tube to close by forming a seam with an A-lattice, in which the protofilaments are staggered by 4.9 nm. Here we show that Mal3, an EB1 family tip-tracking protein, drives tubulin to assemble in vitro into exclusively 13-protofilament microtubules with a high proportion of A-lattice protofilament contacts. We present a three-dimensional cryo-EM reconstruction of a purely A-lattice microtubule decorated with Mal3, in which Mal3 occupies the groove between protofilaments and associates closely with one tubulin monomer. We propose that Mal3 promotes assembly by binding to freshly formed tubulin polymer and particularly favors any with A-lattice arrangement. These results reopen the question of microtubule structure in cells.

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Figure 1: Mal3 promotion of microtubule assembly in vitro.
Figure 2: Mal3 binding to microtubules in vitro.
Figure 3: Microtubules assembled with Mal3 show mixed lattices.
Figure 4: Three-dimensional reconstruction of Mal3-143–decorated A-lattice microtubule.
Figure 5: Model of Mal3 promotion of A-lattice assembly.

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Acknowledgements

The authors thank J. Löwe and the members of his group for their support and comments. This work was supported by the Medical Research Council, Marie Curie Cancer Care and Cancer Research UK.

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Authors and Affiliations

  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK

    Amédée des Georges & Linda A Amos

  2. Molecular Motors Group, Marie Curie Research Institute, The Chart, Oxted, RH8 0TL, Surrey, UK

    Miho Katsuki, Douglas R Drummond, Michael Osei & Robert A Cross

Authors
  1. Amédée des Georges
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  2. Miho Katsuki
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  4. Michael Osei
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Contributions

A.d.G., M.K., D.R.D., R.A.C. and L.A.A. designed the experiments and wrote the manuscript; A.d.G. and M.K. performed the experiments; D.R.D. made strain mmsp174 and plasmid Mal-308; A.d.G. & L.A.A. performed the image analysis; M.O. prepared the S. pombe tubulin.

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Correspondence to Linda A Amos.

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des Georges, A., Katsuki, M., Drummond, D. et al. Mal3, the Schizosaccharomyces pombe homolog of EB1, changes the microtubule lattice. Nat Struct Mol Biol 15, 1102–1108 (2008). https://doi.org/10.1038/nsmb.1482

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