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The peptide sequence TEKKKTRKISQSA corresponds to a phosphorylation hotspot within the cardiac ryanodine receptor (RyR1), a critical intracellular calcium (Ca²⁺) release channel. RyR1 plays a pivotal role in excitation-contraction coupling in cardiac muscle by mediating Ca²⁺ release from the sarcoplasmic reticulum. The phosphorylation of RyR1 at specific sites, including the region represented by this peptide, modulates its activity and is implicated in various cardiac pathologies.
Molecular Details
- Sequence: TEKKKTRKISQSA
- Length: 13 amino acids
- Phosphorylation Sites: The peptide encompasses a region of RyR1 that is phosphorylated by cyclic AMP-dependent protein kinase (PKA). This phosphorylation event is crucial for the regulation of RyR1 activity.
Functional Roles & Mechanism
Phosphorylation of RyR1 at the site corresponding to this peptide sequence enhances the channel's sensitivity to Ca²⁺, facilitating increased Ca²⁺ release during cardiac muscle contraction. This modulation is essential for maintaining proper cardiac rhythm and function. Dysregulation of this phosphorylation event can lead to arrhythmias and other cardiac disorders.
Applications
- Cardiac Research: Understanding the role of RyR1 phosphorylation in cardiac function and its implications in arrhythmogenesis.
- Drug Development: Targeting the phosphorylation site represented by this peptide for therapeutic interventions in cardiac diseases.
- Diagnostic Tools: Developing assays to detect aberrant phosphorylation of RyR1 as biomarkers for cardiac conditions.
References
1. Haji-Ghassemi O, et al. "The Cardiac Ryanodine Receptor Phosphorylation Hotspot." Molecular Cell, 2019. Link
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