Microtubule Sub-Structure and its Role in Protein Binding
2018-07
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Microtubule Sub-Structure and its Role in Protein Binding
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2018-07
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Microtubules are structural polymers that participate in a wide range of cellular functions. The microtubule binding protein EB1 localizes to the growing ends of microtubules, where it facilitates interactions of key cellular proteins with the microtubule plus-end. Recent work has demonstrated that microtubule plus-ends have open, tapered conformations, which diverge greatly from a closed tube conformation. Thus, in this work we explored whether microtubule structure could impact the binding of EB1 to microtubules. Using quantitative fluorescence and electron microcopy experiments, we found that EB1 preferentially binds structurally disrupted or open structural features of microtubules as compared to the closed microtubule lattice. In corresponding 3D single- molecule diffusion simulations, a 70-fold rise in EB1 on-rates to tapered microtubule tip structures was observed relative to a closed lattice conformation, due to a high steric hindrance barrier that impedes EB1 from binding in its four-tubulin pocket-like lattice site, with greatly increased accessibility on two-tubulin protofilament edges at tapered microtubule ends. Thus, EB1’s four-tubulin pocket-like binding site on the microtubule leads to microtubule structural recognition based on a steric-hindrance-mediated on- rate, which may allow the tapered tip structures that are typical at growing microtubule plus ends to assist in facilitating the rapid arrival of EB1 to the microtubule plus-end.
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University of Minnesota Ph.D. dissertation. July 2018. Major: Molecular, Cellular, Developmental Biology and Genetics. Advisor: Melissa Gardner. 1 computer file (PDF); iv, 161 pages.
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Reid, Taylor. (2018). Microtubule Sub-Structure and its Role in Protein Binding. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/216343.
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