Recombinant Human PLN protein

Phospholamban (PLN) is a critical regulatory protein in cardiac muscle cells, primarily involved in calcium homeostasis. It acts as a reversible inhibitor of the sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a), the pump responsible for reuptaking cytosolic calcium into the SR during cardiac relaxation. By binding to SERCA2a, PLN reduces its affinity for calcium, thereby modulating the rate and strength of cardiac contractions. This dynamic regulation is fine-tuned through phosphorylation: when phosphorylated (e.g., by protein kinase A or Ca²⁺/calmodulin-dependent kinase), PLN dissociates from SERCA2a, relieving inhibition and enhancing calcium reuptake, which accelerates relaxation and improves contractility.

Structurally, PLN exists as a monomer or pentamer. The monomeric form is biologically active, while the pentameric form may serve as a storage pool. Its 52-amino-acid sequence includes a transmembrane domain and cytoplasmic regions with phosphorylation sites (Ser16 and Thr17). Mutations in PLN, such as the R14del variant, are linked to inherited cardiomyopathies like dilated cardiomyopathy (DCM) and arrhythmias, highlighting its clinical relevance.

Recombinant PLN protein, produced via bacterial (e.g., E. coli) or eukaryotic expression systems, is widely used to study its biochemical interactions, structural dynamics, and disease-associated mutations. Purified PLN allows in vitro analysis of SERCA2a binding, phosphorylation effects, and screening of therapeutic compounds targeting calcium dysregulation. Engineered variants, including phosphomimetic or dominant-negative mutants, help dissect molecular mechanisms underlying heart failure. Additionally, recombinant PLN supports structural studies (NMR, crystallography) to visualize conformational changes critical for SERCA2a regulation. As a research tool, it bridges molecular insights to potential therapies for calcium-handling disorders, emphasizing its role in both basic science and translational cardiology.