# Functional and molecular mechanisms of human calmodulinopathy in cardiac arrhythmias and sudden cardiac death

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $64,926

## Abstract

Abstract:
 Calmodulin (CaM) is a multifunctional Ca2+ binding protein that plays important roles in a wide range of
intracellular signaling. It orchestrates a number of critical cellular processes. CaM is encoded by 3 distinct
genes in human, namely CALM1, CALM2, and CALM3, each of which encodes for an identical CaM molecule
at the protein level. CaM, a 17 kDa protein comprised of N- and C-terminal lobes linked by a flexible helix.
Each lobe contains two EF hands, canonical Ca2+ binding motifs, with the N-lobe having slightly lower Ca2+
binding affinity. Ca2+ binding to the EF hands results in structural and functional changes of the target
molecules. Recent studies have provided genetics links between human heritable CaM mutations to several
types of cardiac arrhythmias and sudden cardiac death including catecholaminergic polymorphic ventricular
tachycardia (CPVT), long QT syndrome (LQTS), and familial idiopathic ventricular fibrillation (IVF).
 The proposed study will use a combination of computational analyses including Rosetta computational
modeling and molecular dynamics (MD) simulations as well as experimental approaches to decipher the
molecular effects of mutant CaMs, linked to mechanisms of LQTS, on cardiac ion channels including Na+,
Ca2+, and Ca2+-dependent K+ channels. We envision a reiterative process whereby the molecular modeling will
inform the experimental designs and vice versa.

## Key facts

- **NIH application ID:** 10068341
- **Project number:** 1F32HL151130-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Ryan Lee Woltz
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068341

## Citation

> US National Institutes of Health, RePORTER application 10068341, Functional and molecular mechanisms of human calmodulinopathy in cardiac arrhythmias and sudden cardiac death (1F32HL151130-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10068341. Licensed CC0.

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