5VJC

TOG-tubulin binding specificity promotes microtubule dynamics and mitotic spindle formation

Summary for 5VJC

• Entry DOI: 10.2210/pdb5vjc/pdb
• Descriptor: Protein mini spindles (2 entities in total)
• Functional Keywords: tog, heat repeat, tubulin, cell cycle
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 2
• Total formula weight: 62612.81

Authors

Byrnes, A.E.,Slep, K.C. (deposition date: 2017-04-19, release date: 2017-05-10, Last modification date: 2023-10-04)

Primary citation

Byrnes, A.E.,Slep, K.C.
TOG-tubulin binding specificity promotes microtubule dynamics and mitotic spindle formation.
J. Cell Biol., 216:1641-1657, 2017

PubMed Abstract: XMAP215, CLASP, and Crescerin use arrayed tubulin-binding tumor overexpressed gene (TOG) domains to modulate microtubule dynamics. We hypothesized that TOGs have distinct architectures and tubulin-binding properties that underlie each family's ability to promote microtubule polymerization or pause. As a model, we investigated the pentameric TOG array of a XMAP215 member, Msps. We found that Msps TOGs have distinct architectures that bind either free or polymerized tubulin, and that a polarized array drives microtubule polymerization. An engineered TOG1-2-5 array fully supported Msps-dependent microtubule polymerase activity. Requisite for this activity was a TOG5-specific N-terminal HEAT repeat that engaged microtubule lattice-incorporated tubulin. TOG5-microtubule binding maintained mitotic spindle formation as deleting or mutating TOG5 compromised spindle architecture and increased the mitotic index. Mad2 knockdown released the spindle assembly checkpoint triggered when TOG5-microtubule binding was compromised, indicating that TOG5 is essential for spindle function. Our results reveal a TOG5-specific role in mitotic fidelity and support our hypothesis that architecturally distinct TOGs arranged in a sequence-specific order underlie TOG array microtubule regulator activity.

PubMed: 28512144
DOI: 10.1083/jcb.201610090

Experimental method

X-RAY DIFFRACTION (2 Å)