# CRYSTALLOGRAPHY OF MUSCLE REGULATORY PROTEINS

> **NIH NIH R01** · RICE UNIVERSITY · 1992 · $128,189

## Abstract

The goal of this project is to determine three-dimensional structures of
several muscle proteins, with special emphasis on those involved in the
regulation of muscle contraction, and to relate the resulting structures
to physiological events.  Tropomyosin and troponin are key components of
thin-filament based regulation in skeletal muscle and tropomyosin is also
found as a component of actin filaments in a range of smooth muscle and
non-muscle cells.

We are proposing to complete the structural analysis of tropomyosin to
the limit of resolution of the crystals, which is about 3.5 angstroms at
present.  We will construct an atomic model for the protein, and refine
it using restraining methods and/or molecular dynamics.  The resulting
structure will be related to its role in muscle regulation.  We will also
determine low resolution structures of complexes of tropomyosin and
troponin and fragments of actin in the Bailey crystals at low and high
calcium concentrations, to reveal gross changes in the regulatory complex
during activation.

We are proposing to solve the structure of smooth muscle regulatory
complexes, including the tropomyosin-caldesmon complex at low (17
angstrom) resolution to reveal the attachment site of caldesmon on
tropomyosin.  We will also bind caldesmon fragments containing the
putative tropomyosin binding regions of caldesmon in crystals and
determine their binding sites on tropomyosin.  The results will be
compared to those of troponin-containing tropomyosin crystals.

We will also determine the locations of the AMP and ATP sites in
adenylate kinase, and resulting conformational changes that result on
substrate binding, by completing the structure of this enzyme to 2.2
angstroms resolution.  The significance of this work is two-fold.  The
enzyme is a key player in the "energy charge" of the cell, catalyzing the
reaction MgATP + AMP <--> MgADP + ADP.  Furthermore, adenylate kinase is
a close "relative" of one domain of the cystic fibrosis gene product, and
although not implicated in cystic fibrosis, the study of adenylate kinase
may reveal aspects of the function of the cft protein.

## Key facts

- **NIH application ID:** 3156392
- **Project number:** 2R01AR032764-09
- **Recipient organization:** RICE UNIVERSITY
- **SAM.gov UEI:** K51LECU1G8N3
- **Principal Investigator:** GEORGE NEAL PHILLIPS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $128,189
- **Award type:** 2
- **Project period:** 1984-04-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156392

## Citation

> US National Institutes of Health, RePORTER application 3156392, CRYSTALLOGRAPHY OF MUSCLE REGULATORY PROTEINS (2R01AR032764-09). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156392. Licensed CC0.

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