Shelford, J, Burgess, SG, Rostkova, E, Richards, MW, Larocque, G, Sampson, J, Tiede, C, Fielding, AJ, Daviter, T, Tomlinson, DC, Calabrese, AN, Pfuhl, M, Bayliss, R and Royle, SJ (2025) Structural characterization and inhibition of the interaction between ch-TOG and TACC3. The Journal of cell biology, 224 (6). ISSN 0021-9525

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Abstract

The mitotic spindle is a bipolar array of microtubules, radiating from the poles which each contain a centrosome, embedded in pericentriolar material. Two proteins, ch-TOG and TACC3, have multiple functions at the mitotic spindle due to operating either alone, together, or in complex with other proteins. To distinguish these activities, we need new molecular tools to dissect their function. Here, we present the structure of the α-helical bundle domain of ch-TOG that mediates its interaction with TACC3 and a structural model describing the interaction, supported by biophysical and biochemical data. We have isolated Affimer tools to precisely target the ch-TOG-binding site on TACC3 in live cells, which displace ch-TOG without affecting the spindle localization of other protein complex components. Inhibition of the TACC3-ch-TOG interaction led unexpectedly to fragmentation of the pericentriolar material in metaphase cells and delayed mitotic progression, uncovering a novel role of TACC3-ch-TOG in maintaining pericentriolar material integrity during mitosis to ensure timely cell division.

Item Type:	Article
Uncontrolled Keywords:	Hela Cells; Centrosome; Microtubules; Humans; Microtubule-Associated Proteins; Mitosis; Binding Sites; Protein Binding; Models, Molecular; Spindle Apparatus; Microtubule-Associated Proteins; Humans; Spindle Apparatus; Protein Binding; Mitosis; Binding Sites; HeLa Cells; Models, Molecular; Centrosome; Microtubules; 06 Biological Sciences; 11 Medical and Health Sciences; Developmental Biology; 31 Biological sciences; 32 Biomedical and clinical sciences
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	Rockefeller University Press
SWORD Depositor:	A Symplectic
Date Deposited:	21 Mar 2025 16:16
Last Modified:	21 Mar 2025 16:16
DOI or ID number:	10.1083/jcb.202407002
URI:	https://researchonline.ljmu.ac.uk/id/eprint/25960

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