Template-free 13-protofilament microtubule–MAP assembly visualized at 8 A resolution
Fourniol, Franck J. and Sindelar, C.V. and Amigues, B. and Clare, Daniel K. and Thomas, G. and Perderiset, M. and Francis, F. and Houdusse, A. and Moores, Carolyn A. (2010) Template-free 13-protofilament microtubule–MAP assembly visualized at 8 A resolution. The Journal of Cell Biology 191 (3), pp. 463-470. ISSN 0021-9525.
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Microtubule-associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy and single particle algorithms, we solved the 8 Å structure of doublecortin (DCX)-stabilized MTs. Because of DCX’s unusual ability to specifically nucleate and stabilize 13-protofilament MTs, our reconstruction provides unprecedented insight into the structure of MTs with an in vivo architecture, and in the absence of a stabilizing drug. DCX specifically recognizes the corner of four tubulin dimers, a binding mode ideally suited to stabilizing both lateral and longitudinal lattice contacts. A striking consequence of this is that DCX does not bind the MT seam. DCX binding on the MT surface indirectly stabilizes conserved tubulin–tubulin lateral contacts in the MT lumen, operating independently of the nucleotide bound to tubulin. DCX’s exquisite binding selectivity uncovers important insights into regulation of cellular MTs.
|Keyword(s) / Subject(s):||Single-particle structures, Alpha-Beta-Tubulin, Neuronal migration, GTP hydrolysis, lattice seam, doublecortin, mutations, protein, domain, protofilaments|
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Research Centre:||Structural Molecular Biology, Institute of (ISMB)|
|Depositing User:||Sarah Hall|
|Date Deposited:||21 Jun 2012 10:37|
|Last Modified:||06 Dec 2016 11:12|
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