PXD053481

PXD053481 is an original dataset announced via ProteomeXchange.

Title	Mapping the interaction surface between CaVβ and actin and its role in calcium channel clearance
Description	Defective ion channel turnover and clearance of damaged proteins are associated with aging and neurodegeneration. The L-type CaV1.2 voltage-gated calcium channel mediate depolarization-induced calcium signals in heart and brain. Here, we determined the interaction surface between the L-type calcium channel CaVβ subunit and actin using cross-linking mass spectrometry and protein-protein docking, and uncovered a role in replenishing damaged CaV1.2 channels. Computational and in vitro mutagenesis identified hotspots in CaVβ that decrease its affinity for actin but not for CaV1.2. Coexpression of an actin-association-deficient CaVβ mutant with the CaV1.2 channel downregulated current amplitudes with a concomitant reduction in the number of functionally available channels. Neither alterations in the single-channel properties nor changes in the total number of channels at the cell surface were found, indicating that current inhibition resulted from a build-up of conduction-defective channels. Our findings established CaVβ–actin interaction as a key player for selective monitoring and clearing corrupted CaV proteins to ensure the maintenance of a functional pool of channels and proper calcium signal transduction. The CaVβ–actin molecular model introduces a potentially druggable protein-protein interface to intervene CaV-mediated signaling processes.
HostingRepository	PRIDE
AnnounceDate	2025-04-09
AnnouncementXML	Submission_2025-04-09_03:20:22.942.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Beatrix Santiago-Schuebel
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-28 00:24:01	ID requested
⏵ 1	2025-04-09 03:20:23	announced

Dataset with its publication pending

submitter keyword: calcium channel β-subunit, hotspots, cross-linking mass spectrometry, protein-protein docking, CaV1.2 surface expression, actin filaments

Beatrix Santiago-Schübel
contact affiliation	Dr. Beatrix Santiago-Schübel Forschungszentrum Jülich GmbH Insitut für Biologische Informationsprozesse IBI-7: Strukturbiochemie D-52425 Jülich Germany
contact email	b.santiago-schuebel@fz-juelich.de
lab head
Beatrix Santiago-Schuebel
contact affiliation	Forschungszentrum Juelich, ZEA-3
contact email	b.santiago-schuebel@fz-juelich.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053481
     1. Label: PRIDE project
     2. Name: Mapping the interaction surface between CaVβ and actin and its role in calcium channel clearance