1N7L

Solution NMR structure of phospholamban in detergent micelles

1N7L の概要

• エントリーDOI: 10.2210/pdb1n7l/pdb
• 分子名称: Cardiac phospholamban (1 entity in total)
• 機能のキーワード: helix-turn-helix, signaling protein
• 由来する生物種: Oryctolagus cuniculus (rabbit)
• 細胞内の位置: Mitochondrion membrane; Single-pass membrane protein: P61015
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6150.48

構造登録者

Zamoon, J.,Mascioni, A.,Thomas, D.D.,Veglia, G. (登録日: 2002-11-15, 公開日: 2003-10-28, 最終更新日: 2024-05-22)

主引用文献

Zamoon, J.,Mascioni, A.,Thomas, D.D.,Veglia, G.
NMR solution structure and topological orientation of monomeric phospholamban in dodecylphosphocholine micelles.
Biophys.J., 85:2589-2598, 2003

PubMed Abstract: Phospholamban is an integral membrane protein that regulates the contractility of cardiac muscle by maintaining cardiomyocyte calcium homeostasis. Abnormalities in association of protein kinase A with PLB have recently been linked to human heart failure, where a single mutation is responsible for dilated cardiomyopathy. To date, a high-resolution structure of phospholamban in a lipid environment has been elusive. Here, we describe the first structure of recombinant, monomeric, biologically active phospholamban in lipid-mimicking dodecylphosphocholine micelles as determined by multidimensional NMR experiments. The overall structure of phospholamban is "L-shaped" with the hydrophobic domain approximately perpendicular to the cytoplasmic portion. This is in agreement with our previously published solid-state NMR data. In addition, there are two striking discrepancies between our structure and those reported previously for synthetic phospholamban in organic solvents: a), in our structure, the orientation of the cytoplasmic helix is consistent with the amphipathic nature of these residues; and b), within the hydrophobic helix, residues are positioned on two discrete faces of the helix as consistent with their functional roles ascribed by mutagenesis. This topology renders the two phosphorylation sites, Ser-16 and Thr-17, more accessible to kinases.

PubMed: 14507721

実験手法

SOLUTION NMR