# FUNCTIONAL DOMAINS IN CARDIAC TROPONIN C

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 1988 · $103,704

## Abstract

Ca2+-dependent regulation of contraction in striated muscle is
mediated through a heterotrimer called the troponin complex.
Troponin C is the Ca2+-binding subunit of the troponin complex
and is responsible for initial reception of the Ca2+ signal and
transmission of this information through a cascade of myofibril
regulatory and contractile proteins.  The critical role for troponin
C in regulation of muscle contraction emphasizes a need to fully
understand structure/function relationships that enable it to bind
Ca2+ and interact with other troponin subunits in a tissue-specific
manner.  Two isoforms of troponin C exist, one is present in fast
skeletal muscle while the other is found in slow skeletal and
cardiac muscle.  Major regions of sequence divergence between
the isoforms occur in the N-terminal helix and the first Ca2+-
binding loop which is inactive in the cardiac protein.  In this
proposal, molecular biology and recombinant DNA techniques will
be used to generate genes that encode cardiac troponin C with
specific mutations.  The mutant proteins will be produced in
bacteria and characterized in vitro with the goal of identifying
regions that contribute overall function and tissue-specific
characteristics.  Three regions in cardiac troponin C will be
selected for mutagenesis.  First, N-terminal helix, which is
divergent between troponin C isoforms, will be deleted to
determine its participation in the Ca2+-dependent triggering of
the troponin complex.  Second, the inactive first Ca2+-binding
site in cardiac troponin C will be activated and the other three
sites systematically inactivated to determine their relative
contribution to the overall function of the protein.  Finally,
specific acidic amino acids in helices C, D and F will be selected
for mutagenesis to determine if they represent critical sites of
interaction with other troponin subunits.  All mutant proteins will
be characterized for Ca2+-binding properties, alterations inprtein
dynamics and ability to interact with other troponin subunits and
regulate acto-heavy meromyosin ATPase.  Long-term goals will
include characterization of selected mutants by NMR and X-ray
crystallography and transfection of muscle cells in culture with
mutant genes to evaluate structure/function relationships in vivo.
The sum of this information may facilitate the development of
therapeutic agents that modify muscle contraction and possibly
aid in the management of disease states.

## Key facts

- **NIH application ID:** 3159202
- **Project number:** 1R01AR039218-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **SAM.gov UEI:** ZUFBNVZ587D4
- **Principal Investigator:** JOHN Anthony PUTKEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $103,704
- **Award type:** 1
- **Project period:** 1988-02-01 → 1993-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159202

## Citation

> US National Institutes of Health, RePORTER application 3159202, FUNCTIONAL DOMAINS IN CARDIAC TROPONIN C (1R01AR039218-01). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159202. Licensed CC0.

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