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Mitotic spindle association of TACC3 requires Aurora‐A‐dependent stabilization of a cryptic α‐helix
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Burgess, Selena G., Mukherjee, Manjeet, Sabir, Sarah, Joseph, Nimesh, Gutiérrez-Caballero, Christina, Richards, Mark W., Huguenin‐Dezot, Nicolas, Chin, Jason W., Kennedy, Eileen J., Pfuhl, Mark, Royle, Stephen J., Gergely, Fanni and Bayliss, Richard (2018) Mitotic spindle association of TACC3 requires Aurora‐A‐dependent stabilization of a cryptic α‐helix. The EMBO Journal, 37 (8). e97902. doi:10.15252/embj.201797902 ISSN 1460-2075.
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WRAP-mitotic-spindle-TACC3-Aurora‐A‐dependent-Royle-2018.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (3820Kb) | Preview |
Official URL: https://doi.org/10.15252/embj.201797902
Abstract
Aurora‐A regulates the recruitment of TACC3 to the mitotic spindle through a phospho‐dependent interaction with clathrin heavy chain (CHC). Here, we describe the structural basis of these interactions, mediated by three motifs in a disordered region of TACC3. A hydrophobic docking motif binds to a previously uncharacterized pocket on Aurora‐A that is blocked in most kinases. Abrogation of the docking motif causes a delay in late mitosis, consistent with the cellular distribution of Aurora‐A complexes. Phosphorylation of Ser558 engages a conformational switch in a second motif from a disordered state, needed to bind the kinase active site, into a helical conformation. The helix extends into a third, adjacent motif that is recognized by a helical‐repeat region of CHC, not a recognized phospho‐reader domain. This potentially widespread mechanism of phospho‐recognition provides greater flexibility to tune the molecular details of the interaction than canonical recognition motifs that are dominated by phosphate binding.
Item Type: | Journal Article | ||||||||||||||||||||||||
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Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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SWORD Depositor: | Library Publications Router | ||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Cell cycle, Spindle (Cell division), Protein kinases, Phosphorylation | ||||||||||||||||||||||||
Journal or Publication Title: | The EMBO Journal | ||||||||||||||||||||||||
Publisher: | Nature Publishing Group | ||||||||||||||||||||||||
ISSN: | 1460-2075 | ||||||||||||||||||||||||
Official Date: | 13 April 2018 | ||||||||||||||||||||||||
Dates: |
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Volume: | 37 | ||||||||||||||||||||||||
Number: | 8 | ||||||||||||||||||||||||
Article Number: | e97902 | ||||||||||||||||||||||||
DOI: | 10.15252/embj.201797902 | ||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||
Date of first compliant deposit: | 6 June 2018 | ||||||||||||||||||||||||
Date of first compliant Open Access: | 6 June 2018 | ||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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Is Part Of: | NIHR Cambridge Biomedical Research Centre University of Cambridge Hutchison Whampoa Ltd Cancer Research UK (CRUK). Grant Numbers: C24461/A12772, C24461/A23303, C14303/A17043, C25425/A15182 RCUK|Biotechnology and Biological Sciences Research Council (BBSRC). Grant Number: BB/L023113/1 |
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