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An unconventional interaction between Dis1/TOG and Mal3/EB1 promotes the fidelity of chromosome segregation

DOI: 10.1242/jcs.197533 DOI Help

Authors: Yuzy Matsuo (Francis Crick Institute) , Sebastian P. Maurer (The Francis Crick Institute; Barcelona Institute of Science and Technology (BIST)) , Masashi Yukawa (Hiroshima University) , Silva Zakian (The Francis Crick Institute) , Martin R. Singleton (The Francis Crick Institute) , Thomas Surrey (The Francis Crick Institute) , Takashi Toda (The Francis Crick Institute; Hiroshima University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Cell Science

State: Published (Approved)
Published: November 2016
Diamond Proposal Number(s): 13775

Open Access Open Access

Abstract: Dynamic microtubule plus-ends interact with various intracellular target regions such as the cell cortex and the kinetochore. Two conserved families of microtubule plus-end-tracking proteins, the XMAP215, ch-TOG or CKAP5 family and the end-binding 1 (EB1, also known as MAPRE1) family, play pivotal roles in regulating microtubule dynamics. Here, we study the functional interplay between fission yeast Dis1, a member of the XMAP215/TOG family, and Mal3, an EB1 protein. Using an in vitro microscopy assay, we find that purified Dis1 autonomously tracks growing microtubule ends and is a bona fide microtubule polymerase. Mal3 recruits additional Dis1 to microtubule ends, explaining the synergistic enhancement of microtubule dynamicity by these proteins. A non-canonical binding motif in Dis1 mediates the interaction with Mal3. X-ray crystallography shows that this new motif interacts in an unconventional configuration with the conserved hydrophobic cavity formed within the Mal3 C-terminal region that typically interacts with the canonical SXIP motif. Selectively perturbing the Mal3–Dis1 interaction in living cells demonstrates that it is important for accurate chromosome segregation. Whereas, in some metazoans, the interaction between EB1 and the XMAP215/TOG family members requires an additional binding partner, fission yeast relies on a direct interaction, indicating evolutionary plasticity of this critical interaction module.

Journal Keywords: Crystallography; EB1; Microtubule polymerase; TIRF microscopy; XMAP215; TOG

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography


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