# CONFORMATION & RECOGNITION IN MICROTUBLE DYNAMICS

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $343,878

## Abstract

Microtubules (MTs) are essential dynamic polymers required for chromosome segregation and intracellular
organization, and are the direct targets of anti-cancer chemotherapeutics like taxol and the Vinca alkaloids. The
dynamic properties of MTs are central to their function, and they derive from the structural and biochemical
properties of individual tubulin subunits and how they interact within the MT lattice. It is increasingly
appreciated that tubulin subunits adopt distinct conformations as part of the GTPase-dependent
polymerization dynamics, and that regulatory proteins selectively recognize subsets of these conformations to
control MT elongation, stability, and switching. The long-term goal of this research is to build a structural
understanding of how allostery and the tubulin conformation cycle dictate MT dynamics, and of the
mechanisms by which regulatory factors control MT dynamics. In prior project periods, we pioneered a
powerful approach based on structure-inspired site-directed αβ-tubulin mutants. In the present proposal,
through three specific aims, we will build on these themes to provide unique and fundamental new insights
into the physical origins and regulatory mechanism of MT dynamics. We will use biochemistry, reconstitution,
and modeling to define general biochemical mechanisms for XMAP215-family polymerase activity and
processivity. We will reveal through structures how an `allosteric' mutation that alters MT dynamics affects
tubulin conformation in human and yeast MTs, and we will provide new conformation cycle mutants to expand
our understanding of allostery in MT dynamics. Finally, we will identify biochemical and structural design
principles underlying how CLASP TOG interactions with tubulin suppress catastrophe and promote rescue.
This work will provide new information about the conformation(s) of αβ-tubulin and how `allosteric' mutations
can perturb MT dynamics and tubulin conformation. The work will also expand our understanding of how
different TOG domains achieve different regulatory outcomes, with implications for the underlying
mechanisms of microtubule dynamics.

## Key facts

- **NIH application ID:** 10050606
- **Project number:** 2R01GM098543-10
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Luke W Rice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,878
- **Award type:** 2
- **Project period:** 2011-07-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050606

## Citation

> US National Institutes of Health, RePORTER application 10050606, CONFORMATION & RECOGNITION IN MICROTUBLE DYNAMICS (2R01GM098543-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10050606. Licensed CC0.

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