# Structure and function of nonmuscle myosins

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $425,370

## Abstract

Project Summary
A hallmark of eukaryotic cells is their ability to migrate, divide, adhere and respond to environmental cues.
Nonmuscle myosin-2 (NM2) motors play an essential role in many aspects of these fundamental cellular
processes by forming short bipolar filaments that interact with actin filaments. NM2 motors are binary switches
that alter between inactive and active states depending on the cellular context. The precise control of NM2 motor
activity is critical for its cellular function as master regulator of the actin cytoskeleton. Aberrant regulation due to
mutations in NM2 paralogs contribute to a whole host of diseases including blood and neurological disorders,
heart diseases, deafness, nephritis, and cancers. NM2-specific therapies are thus needed, yet the lack of basic
knowledge about the structure and regulation of NM2 paralogs is a bottleneck to their development. We aim to
develop a detailed structural and mechanistic understanding of how force generation by NM2 motors drive
various cellular functions. Using innovative and interdisciplinary techniques including the state-of-the-art cryo-
electron microscopy, X-ray crystallography, steady-state kinetics, in vitro motility assays and high-resolution
fluorescence microscopy, we will systematically dissect the mechanisms of activation and regulation of NM2. To
achieve this, in Aim 1, we will determine the major structural states in the ATPase cycle of NM2 motors to explain
enzyme function. In Aim 2, we will determine a high-resolution cryo-EM structure of the inactive state of full-
length NM2 to explain its molecular architecture. In Aim 3, we will study the consequences of abolishing the
ability to form an inactive state on the dynamics of NM2 filaments in cells. Collectively, our studies will provide a
deeper understanding of the structure, function and regulation of NM2. Importantly, this knowledge will advance
our understanding of emergent NM2 functions in cells and thus, lay the foundation for future development of
NM2-specific therapeutics.

## Key facts

- **NIH application ID:** 10278968
- **Project number:** 1R01GM143539-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** KRISHNA CHINTHALAPUDI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $425,370
- **Award type:** 1
- **Project period:** 2021-08-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10278968

## Citation

> US National Institutes of Health, RePORTER application 10278968, Structure and function of nonmuscle myosins (1R01GM143539-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10278968. Licensed CC0.

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