# L-type Ca2+ Channel Regulation by Calmodulin and CaBP1

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $314,000

## Abstract

The overall objectives are to apply nuclear magnetic resonance (NMR) techniques in
concert with experimental functional approaches to elucidate the molecular structure and regulatory
mechanisms of neuronal L-type voltage-gated Ca2+ channel (CaV1.2) and its atomic-level structural and
functional association with calcium binding protein-1 (CaBP1), -actinin1 (ACTN1) and calmodulin (CaM).
During the next five years, we will use NMR, fluorescence, microcalorimetry, cryoEM, x-ray crystallography,
and computational analysis to delineate the structure and dynamics of CaM and CaBP1 each bound to
CaV1.2. Site-directed mutagenesis and electrophysiology functional analysis will be integrated with atomic–
level structural information to understand how CaM, ACTN1 and CaBP1 each reciprocally control the Ca2+-
dependent channel activity of CaV1.2 in neuronal functions. By pursuing these studies, we hope to gain an
atomic-level understanding of how CaM, ACTN1 and CaBP1 each regulate CaV1.2 involved in controlling
neuronal excitability and gene expression. In particular, we want to understand how protein target
binding sites work in concert with calcium-binding sites to confer Ca2+-dependent channel activity of CaV1.2
at the postsynaptic membrane. This structural information will probe how L-type channel regulation may be
connected to neurological disorders, including epilepsy, Alzheimer’s disease, and Timothy Syndrome.
The Specific Aims are three-fold: (1) Determine the structural basis of CaV1.2 channel activation promoted
by CaM and ACTN1; (2) Elucidate the structure and functional role of a CaM intermediate with 2 Ca2+
bound and determine its role in regulating Ca2+-dependent inactivation (CDI); (3) Determine the structural
basis of how CaBP1 suppresses Ca2+-dependent inactivation (CDI) of CaV1.2.

## Key facts

- **NIH application ID:** 9971387
- **Project number:** 1R01GM130925-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** JAMES B AMES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $314,000
- **Award type:** 1
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971387

## Citation

> US National Institutes of Health, RePORTER application 9971387, L-type Ca2+ Channel Regulation by Calmodulin and CaBP1 (1R01GM130925-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971387. Licensed CC0.

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