# MUSCLE REGULATORY SYSTEM

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 1990 · $145,396

## Abstract

Muscular contraction is initiated by calcium binding to troponin C
in skeletal and cardiac muscles.  This binding triggers a series of
molecular events which ultimately lead to the cyclic interaction
between myosin and actin as ATP is hydrolyzed.  This cyclic
interaction results in development of tension.  The long-term goal
of our research program is to understand how the calcium signal is
transmitted from its site at troponin C to several other proteins.
This signal transmission is fundamental to the overall regulatory
mechanism.  The approaches taken in this proposal are based on a
combination of energetic analysis of multiple-ligand interactions
involving calcium and the various proteins that comprise the
muscle thin filament and structural perturbations on these
proteins induced by calcium binding to troponin C.  Proteins that
are specifically altered in their sequence and synthetic
oligopeptides will be used to assist in delineating alternative
routes for information transfer.  The methodologies chosen for
these studies include steady state fluorimetry, time-resolved
millisecond, nanosecond, and picosecond fluorescence
spectroscopy, stopped-flow kinetic technique, and other physical
methods.  The role of tryptophanyl and tyrosyl residues in signal
transfer will be studied through analysis of their emission decay
and anisotropy decay.  The rapid molecular motions of these
residues in troponin C, calmodulin and possibly other proteins will
be compared with simulation results based on molecular dynamics.
Moleculare distances will be determine by fluorescence resonance
energy transfer and will serve to report on global structural
perturbations that occur when actomysosin ATPase is activated.
The relevance of these changes in calcium regulation will be
investigated by rapid kinetics techniques.  Finally, a comparison
will be made between cardiac regulatory proteins and skeletal
regulatory proteins in terms of the energetics of multiple-ligand
binding and the nature and extent of structural perturbations that
can be correlated with functional properties.

The proposed studies are expected to advance our knowledge in
signal transmission in muscle and contribute toward our
understanding of the role of multiple-ligand binding in biological
regulation.  The proposed work will also enhance our knowledge of
the role of very rapid molecular motions in biological functions.

## Key facts

- **NIH application ID:** 3155277
- **Project number:** 5R01AR025193-12
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **SAM.gov UEI:** YND4PLMC9AN7
- **Principal Investigator:** HERBERT C CHEUNG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $145,396
- **Award type:** 5
- **Project period:** 1979-09-25 → 1992-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155277

## Citation

> US National Institutes of Health, RePORTER application 3155277, MUSCLE REGULATORY SYSTEM (5R01AR025193-12). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155277. Licensed CC0.

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