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Contenu archivé le 2024-05-14

Analysis of the interaction of calmodulin and fkb12 with the mh defective ryanodine receptor channel 5

Objectif



The RYR1 protein is the main Ca2+ release channel in skeletal muscle SR. Mutations in the gene for this channel are known to cause the inherited syndrome malignant hyperthermia (MH) and make the channel more sensitive to activation by a number of agonists including Ca2+, caffeine, ATP and halothane. In vivo, the RYR1 channel interacts with a number of protein modulators including the irnmunophilin FKBP-12 and calmodulin proteins. In this project I will investigate the effects of RYR1 mutations on interaction of the channel with protein modulators. Specifically, I will use Ca2+ efflux, ligand binding, protein purification, imrnunological detection methods and electrophysiological approaches to perform detailed analysis of calmodulin activation / modulation of, and FKBP 12 interaction with, and modulation of, the normal and mutant RYR1 channels. The results obtained will for the first time provide significant information on the effect of MH mutations on channel modulation by these two associated proteins.

Champ scientifique (EuroSciVoc)

Programme(s)

Thème(s)

Appel à propositions

Données non disponibles

Régime de financement

RGI - Research grants (individual fellowships)

Coordinateur

Universität Ulm
Contribution de l’UE
Aucune donnée
Adresse
Albert-Einstein-Allee 11
89081 Ulm
Allemagne
Coût total
Aucune donnée

Participants (1)