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Nature 435, 523-527 (26 May 2005) | doi:10.1038/nature03586; Received 10 December 2004; Accepted 31 March 2005

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Insights into microtubule nucleation from the crystal structure of human big gamma-tubulin

Hector Aldaz1,4,3, Luke M. Rice1,4, Tim Stearns2 & David A. Agard1

  1. Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, California 94143, USA
  2. Department of Biological Sciences, Stanford University, Stanford, California 94305-5020, USA
  3. †Present address: Department of Molecular and Cell Biology, University of California, Berkeley, 16 Barker Hall, Berkeley, California 94720-3202, USA
  4. *These authors contributed equally to this work

Correspondence to: David A. Agard1 Correspondence and requests for materials should be addressed to D.A.A. (Email: agard@msg.ucsf.edu).

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Microtubules are hollow polymers of alphabeta-tubulin that show GTP-dependent assembly dynamics and comprise a critical part of the eukaryotic cytoskeleton. Initiation of new microtubules in vivo requires gamma-tubulin, organized as an oligomer within the 2.2-MDa gamma-tubulin ring complex (gamma-TuRC) of higher eukaryotes1, 2, 3. Structural insight is lacking regarding gamma-tubulin, its oligomerization and how it promotes microtubule assembly. Here we report the 2.7-Å crystal structure of human gamma-tubulin bound to GTP-gammaS (a non-hydrolysable GTP analogue). We observe a 'curved' conformation for gamma-tubulin–GTPgammaS, similar to that seen for GDP-bound, unpolymerized alphabeta-tubulin4. Tubulins are thought to represent a distinct class of GTP-binding proteins, and conformational switching in gamma-tubulin might differ from the nucleotide-dependent switching of signalling GTPases. A crystal packing interaction replicates the lateral contacts between alpha- and beta-tubulins in the microtubule5, and this association probably forms the basis for gamma-tubulin oligomerization within the gamma-TuRC. Laterally associated gamma-tubulins in the gamma-TuRC might promote microtubule nucleation by providing a template that enhances the intrinsically weak lateral interaction between alphabeta-tubulin heterodimers. Because they are dimeric, alphabeta-tubulins cannot form microtubule-like lateral associations in the curved conformation5. The lateral array of gamma-tubulins we observe in the crystal reveals a unique functional property of a monomeric tubulin.

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