# NEUTRON DIFFRACTION STUDIES OF MUSCLE CONTRACTION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1990 · $283,444

## Abstract

The long-term objective of the proposed work is to understand the
molecular basis of the mechanism of muscle contraction.  This will
involve understanding how ATP hydrolysis is coupled to the large-
scale macro-molecular changes responsible for force generation and
how the changes are regulated.  This work, which has a basic
science objective, will generate knowledge which may have
implications for cardiac and muscle-related disease.

We proposed using neutron solution scattering and neutron helical
diffraction to investigate specific structural questions crucial
to the understanding of how muscle works.  The experiments will
utilize the selective deuteration of one, or sometimes two, of the
members of the macromolecular complex under study.  By varying
buffer D2O content, contrast-matching of the buffer with protonated
(H) or deuterated (D) protein will be achieved.  This will allow
examinations of unmatched protein (either H or D) in situ with
little or no interference from the other ("invisible") proteins.
Deuterated proteins will be generated by cell biology and
recombinant DNA techniques.

We will investigate the following questions:  (1) What is the in
situ structure of regulatory light chains (RLC's) of myosin when
the myosin heads are either free in solution or bound to actin with
and without Ca2+?  What is the separation of RLC's when heads ar
bound to actin?  (2) What is the in situ structure of troponin-C
(TNC) with and  without bound Ca2+ and what is the cross-helix
radial separation of TNC with and without bound Ca2+?  Is the TNC-
TNC separation affected by myosin binding to the thin filament?
(3) What are the structural changes, if any, that occur in the thin
filament when myosin heads bind to actin in the absence of ATP?
(4) What is the position and separation of RLC in relaxed, rigor,
the putative weak-binding state and in an analog-induced state
thought to resemble a force generating acto-myosin intermediate?
(5) What is the change in position and intra-myosin separation of
light chains when muscles are stretched in rigor?  (6) What is the
average radial position of the light chain-bearing portion of the
myosin head in a muscle during isometric contraction of muscle
fibers?  Does the intensity of the 14.3 mn meridional reflection
(arising from light chains alone) increase during contraction as
it does in X-ray diffraction?  (7) What are the phases of the
equatorial neutron diffraction pattern from rigor vertebrate
muscle?  Can the low-resolution structure of rigor muscle fibers
be determined from neutron diffraction?

The answers to these questions will test hypotheses about how
muscle contraction and regulation occur.

## Key facts

- **NIH application ID:** 3159925
- **Project number:** 5R01AR039710-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** ROBERT A MENDELSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $283,444
- **Award type:** 5
- **Project period:** 1989-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159925

## Citation

> US National Institutes of Health, RePORTER application 3159925, NEUTRON DIFFRACTION STUDIES OF MUSCLE CONTRACTION (5R01AR039710-02). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159925. Licensed CC0.

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