# NIH grant: AI-guided structural biology of Cav1.2 (1R03HL183019-01) — retained record

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source: [us-gov-api](https://highsignal.app/data/us-gov-api) (us-gov-api:nih-reporter)  published 2026-06-18 00:00 ingested 2026-06-28 12:46

[original source ↗](https://reporter.nih.gov/project-details/1R03HL183019-01)

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NIH grant 1R03HL183019-01: AI-guided structural biology of Cav1.2
Institute: {'code': 'HL', 'abbreviation': 'NHLBI', 'name': 'National Heart Lung and Blood Institute', 'admin_org_id': '12500068', 'admin_funding_url': ''}. PI: MICHAEL J LENAEUS. Award: $233250.
Start: 2026-06-18T00:00:00.
Project Summary/Abstract
 The L-type calcium channel Cav1.2 plays a critical role in excitation-contraction coupling in the heart. Its
calcium flux generates the plateau phase of the cardiac action potential and results in the calcium-induced
calcium release needed to trigger cardiac contractions. Cav1.2 is a multi-subunit protein consisting of a large,
transmembrane 1 subunit and smaller, auxiliary subunits important for trafficking and channel regulation.
Recent cryogenic electron microscopy (cryo-EM) experiments have revealed much of the three-dimensional
structure of Cav1.2’s core domains, though the final 571 residues of the 1 subunit’s intracellular C-terminal
domain (CTD) have not yet been resolved despite key regulatory roles in channel function. This domain has
been shown to be important for Cav1.2’s regulation by calcium/calmodulin and has an important role in cross-
talk between Cav1.2 and the sympathetic nervous system, amongst other cell signaling pathways. In this
proposal, I will use insights from artificial intelligence to develop a platform for CTD structural biology, then
validate that platform by measuring its ability to form protein-protein interactions with known binding partners of
Cav1.2, including calcium/calmodulin and an autoregulatory distal C-terminal fragment. If successful, I will also
attempt crystallization of the CTD in complex with several binding partners. Together these data will provide the
starting point for future structural biology projects on Cav1.2 regulation and protein-protein interactions.
```



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