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Comparing the structure and dynamics of phospholamban pentamer in its unphosphorylated and pseudo‐phosphorylated states
Author(s) -
Oxenoid Kirill,
Rice Amanda J.,
Chou James J.
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.072975107
Subject(s) - phospholamban , pentamer , serca , phosphorylation , endoplasmic reticulum , chemistry , biophysics , calcium binding protein , phosphoprotein , atpase , calcium , biochemistry , biology , organic chemistry , enzyme
Human phospholamban (PLN), a 30 kDa homopentamer in the sarcoplasmic reticulum (SR) membrane, controls the magnitude of heart muscle contraction and relaxation by regulating the calcium pumping activity of the SR Ca 2+ ‐ATPase (SERCA). When PLN is not phosphorylated, it binds and inhibits SERCA. Phosphorylation of PLN at S16 or T17 releases such inhibitory effect. It remains a matter of debate whether phosphorylation perturbs the structure of PLN, which in turn affects its interaction with SERCA. Here we examine by NMR spectroscopy the structure and dynamics of PLN pentamer with a physiologically relevant, phosphorylation‐mimicking mutation, S16E. Based on extensive NMR data, including NOEs, dipolar couplings, and solvent exchange of backbone amides, we conclude that the phosphorylation‐mimicking mutation does not perturb the pentamer structure. However, 15 N R 1 and R 2 relaxation rates and 15 N( 1 H) NOEs suggest subtle differences in the dynamics of the extramembrane portion of the protein.