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- W2030603906 abstract "Phospholamban (PLN), an amphipathic intrinsic membrane protein of 52 amino acids, is the modulator of the Ca2+ pump of cardiac, slow-twitch, and smooth-muscle sarcoplasmic reticulum. In response to β-adrenergic stimulation, it becomes phosphorylated at Ser16 and/or Thr17, and dissociates from the pump, which, in turn, achieves its full activity. Here we present the three-dimensional structure of chemically synthesized, monomeric PLN in an organic solvent. Monomerization (PLN normally forms homopentamers) was obtained by replacing Cys41 with phenylalanine (Phe=F), a modification that did not affect biological activity. The structure was determined by high-resolution NMR in CHCl3/MeOH of the unphosphorylated state of [F41]PLN (C41F). Of the hydrophilic cytoplasmic parts IA (Met1 to Pro21) and IB (Gln22 to Asn30) and the membrane-spanning hydrophobic domain II (Leu31 to Leu52) of PLN, domain IA, which contains the two phosphorylation sites Ser16 and Thr17, and domain II have been suggested to be helical and connected through the less-structured hinge-region IB. In the structural study presented here, [F41]PLN is composed of two α-helical regions connected by a β-turn (type III). The residues of the β-turn (type III) are Thr17, Ile18, Glu19, and Met20, the first being one of the two phosphorylation sites (Ser16 and Thr17). The hinge region is located at the C-terminal end of domain IA, and domain IB is part of a second helix. The two α-helices comprising amino acids 4 – 16 and 21 – 49 are well-defined (the root-mean-square deviations for the backbone atoms, calculated for a family of the structures, are 0.58 and 0.92 Å, resp.). Pro21 is at the beginning of the C-terminal helix and in the trans conformation." @default.
- W2030603906 created "2016-06-24" @default.
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- W2030603906 date "2000-09-06" @default.
- W2030603906 modified "2023-10-15" @default.
- W2030603906 title "NMR Solution Structure of Phospholamban" @default.
- W2030603906 doi "https://doi.org/10.1002/1522-2675(20000906)83:9<2141::aid-hlca2141>3.0.co;2-w" @default.
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