# STRUCTURAL STUDIES ON MOLECULAR TRACKS AND MOTORS

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1993 · $226,434

## Abstract

The long term goal of the work is to understand in structural terms the
mechanism of action of the molecular tracks (F-actin and microtubules)
and motors (myosin, kinesin, dynein) responsible for motility in the
cell.  Achieving this goal will ultimately require a synthesis of results
obtained by two complementary methods:  X-ray crystallography will
provide detailed atomic information on the individual proteins and is
being carried out in other labs.  Cryo-EM and image analysis will provide
details of the tertiary and quaternary structure and will show how the
individual molecules fit together into the working assemblies found in
the cell.  Described herein is the application of this later approach to
acto-myosin systems together with an investigation of the structural
basis for dynamic instability in microtubules.

Three types of information are essential for building the functional
assemblies from the atomic structures of the individual proteins:  (i)
the molecular envelope of the assembly, (ii) the locations of the
individual proteins within the assembly and (iii) the locations of
surface markers on specific proteins.

Completion of the following experiments, together with data already
collected, will provide all three types of information for the rigor
complex of F-actin and the myosin head.  In addition, unique information
on the mechanism of both actin-based and myosin-based regulation will be
obtained.

Gold-cluster labelling will be used to locate specific surface residues
on the myosin head in decorated filaments.

The 3-D structures of single-headed HMM-decorated actin and of
crystalline arrays of a myosin I will be determined to provide
information on the conformation of the light-chain-containing region of
the myosin head.

To complete our work on the mechanism of thin filament-based regulation,
the structure of F-actin complexed with selected regulatory proteins will
be determined.

To describe conformational changes occurring in myosin-based regulation,
the structure of activated and regulated brush border myosin I complexes
to F-actin will be compared.

Correlation of 3D EM data with the atomic model of F-actin will be
carried out in collaboration with Ken Holmes.

Preliminary data on microtubules suggest a structural explanation for
their dynamic instability.  This hypothesis will be tested in simple
experiments using non-hydrolyzable GTP analogues.

## Key facts

- **NIH application ID:** 3159125
- **Project number:** 2R01AR039155-06
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **SAM.gov UEI:** PHZJFZ32NKH4
- **Principal Investigator:** RONALD A MILLIGAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $226,434
- **Award type:** 2
- **Project period:** 1988-02-01 → 1998-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159125

## Citation

> US National Institutes of Health, RePORTER application 3159125, STRUCTURAL STUDIES ON MOLECULAR TRACKS AND MOTORS (2R01AR039155-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159125. Licensed CC0.

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