| Autor: |
Burgess, Selena G., Mukherjee, Manjeet, Sabir, Sarah, Joseph, Nimesh, Gutiérrez‐Caballero, Cristina, Richards, Mark W., Huguenin‐Dezot, Nicolas, Chin, Jason W., Kennedy, Eileen J., Pfuhl, Mark, Royle, Stephen J., Gergely, Fanni, Bayliss, Richard |
| Předmět: |
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| Zdroj: |
EMBO Journal; 4/13/2018, Vol. 37 Issue 8, p1-1, 20p, 6 Diagrams, 1 Chart, 2 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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