# Diversity Supplement to Mechanisms of Thin Filament Regulation by Myosin Binding Protein-C

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2022 · $25,464

## Abstract

PROJECT SUMMARY
The goal of this supplement is to support diversity in NIH missions through training and mentoring a
graduate student with a disability. Research proposed under this supplement will be an integral part of
the parent m-PI R01 (HL140925) and will be performed in the laboratory of Dr. Samantha Harris, one
of the m-PIs, at the University of Arizona. Briefly, goals of the parent R01 are aimed at determining the
structure-function relationships of cardiac myosin binding protein-C (cMyBP-C), an essential regulator
of heart function, in its interactions with target proteins on the thin filaments of muscle sarcomeres.
Specifically, high resolution cryo-EM reconstructions are created that yield information regarding the
precise residues and binding interfaces for each of the N’-terminal subdomains of cMyBP-C with
proteins on the thin filament (actin, tropomyosin, and troponin). The functional significance of these
interactions is then determined using site directed mutagenesis to disrupt or strengthen these
interactions followed by assessment of protein function in biochemical assays and force measurements
in permeabilized (“skinned”) cardiac muscle cells. The proposed research will contribute to the aims of
the parent award by 1) investigating the functional significance of amino acids in the “R-A-S-K” loop of
domain C1 on force because these residues were shown by cryo-EM to activate the thin filament; 2)
determining the functional effects of phosphorylation at each of the 3 canonical serines, individually
and in aggregate, in the regulatory M-domain of cMyBP-C. These experiments are entirely within the
scope of the parent proposal, but were chosen as ideal subprojects for mentoring and training a new
graduate student to become proficient in technically challenging measurements of force in detergent-
permeabilized muscle cells. Results from this funding will therefore increase inclusion and diversity
while advancing the aims of the parent proposal by investigating key regulatory effects of cMyBP-C.

## Key facts

- **NIH application ID:** 10489508
- **Project number:** 3R01HL140925-04S1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Vitold Galkin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $25,464
- **Award type:** 3
- **Project period:** 2018-12-17 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489508

## Citation

> US National Institutes of Health, RePORTER application 10489508, Diversity Supplement to Mechanisms of Thin Filament Regulation by Myosin Binding Protein-C (3R01HL140925-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10489508. Licensed CC0.

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