Structural State Recognition Facilitates Tip Tracking of EB1 at Growing Microtubule Ends

Overview

Journal Elife

Specialty Biology

Date 2019 Sep 4

PMID 31478831

Citations 16

Authors

Taylor A Reid

Courtney Coombes

Soumya Mukherjee

Rebecca R Goldblum

Kyle White

Sneha Parmar

Mark McClellan

Marija Zanic

Naomi Courtemanche

Melissa K Gardner

Affiliations

Soon will be listed here.

Abstract

The microtubule binding protein EB1 specifically targets the growing ends of microtubules in cells, where EB1 facilitates the interactions of cellular proteins with microtubule plus-ends. Microtubule end targeting of EB1 has been attributed to high-affinity binding of EB1 to GTP-tubulin that is present at growing microtubule ends. However, our 3D single-molecule diffusion simulations predicted a ~ 6000% increase in EB1 arrivals to open, tapered microtubule tip structures relative to closed lattice conformations. Using quantitative fluorescence, single-molecule, and electron microscopy experiments, we found that the binding of EB1 onto opened, structurally disrupted microtubules was dramatically increased relative to closed, intact microtubules, regardless of hydrolysis state. Correspondingly, in cells, the blunting of growing microtubule plus-ends by Vinblastine was correlated with reduced EB1 targeting. Together, our results suggest that microtubule structural recognition, based on a fundamental diffusion-limited binding model, facilitates the tip tracking of EB1 at growing microtubule ends.

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