# CRYO-ELECTRON MICROSCOPY OF MUSCLE FILAMENTS

> **NIH NIH R01** · SCRIPPS CLINIC AND RESEARCH FOUNDATION · 1989 · $115,534

## Abstract

The long term objectives of this work are to define accurately the
structural relationships of actin, myosin Sl and tropomyosin from
vertebrate striated muscle.  The goals of the research proposed
are to identify the actin moiety in Sl decorated filaments.  To
determine the magnitude and direction of the movement of
tropomyosin during thin filament activation and to provide
accurate maps of the decorated filament for future modelling
studies with the high-resolution X-ray maps.

To accomplish these goals, 3-D maps of F-actin and of thin
filaments (actin, tropomyosin and the troponin complex) in the
presence and absence of Ca2+ will be calculated and compared
with each other and with already-completed maps of Sl decorated
filaments.  An adequate method to correct the data for the
effects of the contrast transfer function of the microscope will be
devised.

The research will be undertaken according to the following plan:
(1) Exploration of conditions for optimum preservation of the
filaments.  (2) Biochemical assessment to thin filament function
under these conditions.  (3) Collection, computer processing and
averaging of data to provide 3-D maps of F-actin and thin
filaments (+ and - Ca2+).  (4) Comparison of these maps with
already completed maps of the decorated filaments to:  (i.)
identify the actin moiety in decorated filaments (ii.) define the
effect of Sl binding on the position of tropomyosin in the presence
of Ca2+ (iii.) determine the magnitude of the movement of
tropomyosin in thin filaments in response to Ca2+ binding by the
troponin complex (iv.) explore the consequences of these findings
for current models for Ca2+ mediated thin filament regulation of
muscular contraction.  (5) TMV will be used as a model system to
explore the effects of the contrast transfer function.

The techniques to be used have been applied successfully with Sl
decorated filaments and include cryo-electron microscopy and
computer processing and averaging of images.

## Key facts

- **NIH application ID:** 3159126
- **Project number:** 5R01AR039155-02
- **Recipient organization:** SCRIPPS CLINIC AND RESEARCH FOUNDATION
- **Principal Investigator:** RONALD A MILLIGAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $115,534
- **Award type:** 5
- **Project period:** 1988-02-01 → 1993-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159126

## Citation

> US National Institutes of Health, RePORTER application 3159126, CRYO-ELECTRON MICROSCOPY OF MUSCLE FILAMENTS (5R01AR039155-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159126. Licensed CC0.

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