# STRUCTURE FUNCTION RELATIONS IN MYOSIN

> **NIH NIH R01** · BOSTON BIOMEDICAL RESEARCH INSTITUTE · 1992 · $212,381

## Abstract

Elucidation of the mechanism of muscle contraction requires further
information concerning structure- function relationships in the myosin
head (S1), the key regions containing the actin and nucleotide interaction
sites.  Knowledge of the precise mode of subunit interactions within the
myosin molecule as well as the process of assembly of myosin molecules by
interaction of their coiled-coil portions into thick filaments is also
incomplete.  Thus the application is focusing on four areas: (1) The
topography of myosin S1 will be explored by (a) establishing proximity
relationships in myosin S1 with the use of photoactivatable crosslinkers
under various conditions (in the presence of nucleotide, actin, etc.); (b)
elucidating the process of polypeptide chain unfolding under partial
denaturation conditions such as methanol or heat treatment; (c) studying
the effects and locations of antibodies made against specific segments of
peptides of S1. (2) The interaction of actin and myosin will be explored
by (a) identifying the regions within the interface between actin and S1
after crosslinking under conditions corresponding to strong and weak
binding states; (b) using synthetic peptides with sequences corresponding
to the putative binding regions of S1 and actin; (c) using actin mutants
with thiols introduced at the putative interfaces by site directed
mutagenesis. (3) The mechanism of thick filament formation by myosin rod
association including parallel and anti-parallel packing will be studied
by crosslinking the filaments with the zero length crosslinker 1-ethyl-3-
[3- (dimethyl amino) propyl] carbodiimide (EDC) or with thiol specific
reagents.  New thiols will be introduced by genetic engineering, which
would permit the attachment of fluorescent probes or crosslinkers at
desired locations. (4) The light chain/ heavy chain interaction will be
studied by identifying the regions involved in the crosslinking between
heavy chain and alkali light chains with EDC and N-hydroxy succinimide.
We will also crosslink light chains to heavy chains with thiol specific
photoactivatable reagents using hybrid S1 with light chains from different
species or light chains, expressed after site directed mutagenesis.  The
knowledge of nomal muscle will serve as a reference and may eventually
prove useful in the diagnosis, treatment, and prevention of disease
involving muscle tissues and the cardiovascular system.

## Key facts

- **NIH application ID:** 3155643
- **Project number:** 5R01AR028401-10
- **Recipient organization:** BOSTON BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** RENNE C LU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $212,381
- **Award type:** 5
- **Project period:** 1991-09-20 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155643

## Citation

> US National Institutes of Health, RePORTER application 3155643, STRUCTURE FUNCTION RELATIONS IN MYOSIN (5R01AR028401-10). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155643. Licensed CC0.

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