# Structure and Function of Myosin VI

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $351,056

## Abstract

Summary/Abstract:
The characterization of myosin VI has generated a number of paradigm shifting concepts leading to the
proposal that a subset of myosin classes form folded, inactive monomers until binding partner engagement
induces activation. This binding additionally triggers dimerization (i.e. cargo-initiated dimerization) for at least
three classes of myosin (VI, VIIA, and X), which are the focus of this proposal. While folding forms the basis of
regulation of two-headed myosins from class II and V, the novel form of regulation found in class VI, VIIA, and
X myosins can allow these myosins to diffuse throughout the cell as compact, folded monomers until they
encounter their binding partners. Since most of the cellular functions served by these myosins are at the cell
periphery, either in the cortical actin or in actin extensions, this may allow efficient delivery through dense actin
networks. Two of the classes appear to be optimized for movement on bundles of actin (VIIA and X), while
myosin VI traffics optimally on single actin filaments. Our most recent results suggest that all three classes
share another feature, namely an anti-parallel coiled coil, which has not been described in any other myosin
classes. This places the heads of the dimer in a geometry that may optimize their trafficking. We will probe the
key features of these myosin classes with a combination of kinetic, single molecule, structural, and cell
biological studies.
In addition to sharing a common form of regulation, both class VI and VIIA myosins are involved in the
assembly and maintenance of strereocilia of the cochlear hair cells. Mutations in these myosins lead to
deafness. We will initiate the development of molecules that may be able to counter the impact of some of
these deafness mutations.

## Key facts

- **NIH application ID:** 9940710
- **Project number:** 5R01DC009100-18
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** H Lee Sweeney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,056
- **Award type:** 5
- **Project period:** 2002-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9940710

## Citation

> US National Institutes of Health, RePORTER application 9940710, Structure and Function of Myosin VI (5R01DC009100-18). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9940710. Licensed CC0.

---

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