# Structural basis of motility by dimeric kinesin and myosin motor proteins

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $339,905

## Abstract

Project Summary
Kinesin and myosin are so-called `motor proteins' that can use two `feet' to walk along
microtubule and actin filaments (respectively) that make up the cytoskeleton. These motors
support many vital functions with the cell, including pulling DNA structures apart during cell
division and resupplying nerve junctions (the synapse) with neurotransmitters (such as
seratonin). The precise mechanisms by which these elaborate molecular machines, which are
composed of tens of thousands of exquisitely arranged atoms, are able to `walk' are complex
and incompletely understood. To see how they work, it is necessary to visualize these complex
structures in three dimensions at sufficient levels of detail to resolve individual atoms– and to
follow molecular rearrangements that happen while the motors step forward. This goal,
however, has long remained out of reach due to the extreme technical challenges involved.
We have addressed this problem by developing new methods to analyze images of frozen
motor-filament assemblies collected by latest-generation electron microscopes. This approach,
known as cryo-electron microscopy, allows us to directly visualize the three dimensional shape
of individual molecular motor proteins attached to their partner filaments.
During the previous funding period, we solved 3D structures of truncated single `feet' (one motor
domain) of kinesin and myosin motors attached to their partner filaments, showing in atomic
detail how these structures changed when molecules of ATP fuel were bound and consumed.
We also captured a 3D structure of an intact pair of kinesin molecules (dimer) caught in mid-
step on a microtubule. This allowed us to visualize, for the first time, a way in which the two
`feet' of kinesin can pull on each other in a way to stay coordinated while walking. In our ongoing
research we are improving our methods to capture more intermediates in the stepping process
of kinesin, in order to gain a complete more understanding of how it walks. We are improving
our analysis methods to better resolve precise chemical details within these structures. Finally,
we are extending our approach to understand how a pair of myosin molecules can walk along
the actin filament. Results of our studies are expected to aid the development of a new
generation of pharmaceutical agents for treating cancer and a wide variety of other diseases.

## Key facts

- **NIH application ID:** 9887049
- **Project number:** 2R01GM110530-06
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** CHARLES VAUGHN SINDELAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,905
- **Award type:** 2
- **Project period:** 2014-05-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9887049

## Citation

> US National Institutes of Health, RePORTER application 9887049, Structural basis of motility by dimeric kinesin and myosin motor proteins (2R01GM110530-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9887049. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*