# EM Studies on Muscle

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2020 · $378,286

## Abstract

Project Summary
The long term goal of this research project is to understand the molecular mechanism of force production
through 3-D visualization of myosin molecular motors in situ in muscle. The research focuses on the structure
of the large waterbug Lethocerus sp. because its filament lattice is the best ordered of all known muscles types
thereby making it an excellent candidate for 3-D imaging as well as facilitating the trapping of many myosin
motors into similar states. Lethocerus, like many insects, utilize a stretch activation mechanism to operate their
flight muscles. Stretch activation also occurs in vertebrate striated and cardiac muscle, where in the case of
cardiac muscle, it is an important part of the rhythmic contractions. Recent advancements in detector
technology, robotic electron microscopes and high throughput data collection, have made it possible to image
the filaments themselves at atomic or near atomic resolution thereby providing unprecedented opportunity for
atomic level interpretation of muscle. In the current funding period, we have obtained unprecedented
resolution and detail of the relaxed state of thick filaments from Lethocerus flight muscle. No coiled-coil
protein of the size of myosin has been imaged previously at the resolution we have achieved at the moment
(4.3Å) in the backbone of the myosin filament. No assembly of coiled-coiled proteins of the size of the myosin
filament backbone has been imaged at this resolution. This advance provides opportunity to investigate the
mechanism whereby myosin rod mutations can affect muscle function. The head folding of myosin II
filaments of smooth and non-muscle leads to filament instability. This phenomenon has been hypothesized to
be due to changes in the rod structure brought on by the head folding. Put simply, the structure of the myosin
rod and the myosin heads are coupled in some way, possibly through the transmission of torsional motions of
the heads through the coiled-coil rod. Reversing that logic, a change in the coiled-coil structure of packing in
the backbone could affect the head folding. Recent muscle research has pointed to the possibility that tension
applied either internally by myosin heads or externally by a stretch, can affect the structure of the myosin
heads. Thus, the thick filament may function as a tension transducer, but the molecular mechanism by which
this occurs in unknown. We hypothesize that tension applied to the thick filament affects the structure of the
myosin heads and vice versa, that the myosin heads affect the structure of the myosin rods. We can now test
this hypothesis in a naturally formed filament by improving the order of the myosin heads in a relaxed thick
filament followed by imaging by cryoEM to obtain better information on the position of the coiled-coil side
chains. If the heads and coiled-coil rod structures are coupled, then disordering or removing the relaxed heads
of Lethocerus thick filaments, followed by 3D imaging sho...

## Key facts

- **NIH application ID:** 9904658
- **Project number:** 5R01GM030598-32
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** KENNETH ALLEN TAYLOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,286
- **Award type:** 5
- **Project period:** 1982-05-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904658

## Citation

> US National Institutes of Health, RePORTER application 9904658, EM Studies on Muscle (5R01GM030598-32). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9904658. Licensed CC0.

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