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The role of phosphorylation on the structure and dynamics of phospholamban: A model from molecular simulations
Author(s) -
Pantano Sergio,
Carafoli Ernesto
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21239
Subject(s) - phospholamban , chemistry , phosphorylation , biophysics , serca , molecular dynamics , cytoplasm , transmembrane domain , membrane , endoplasmic reticulum , phospholipid , transmembrane protein , cardiac muscle , crystallography , biochemistry , computational chemistry , biology , atpase , receptor , enzyme , endocrinology
Phospholamban (PLB) is a small membrane protein that regulates the activity of the calcium ATP‐ase in the cardiac, slow‐twitch, and smooth muscle sarcoplasmic reticulum through the reversible phosphorylation of Ser16. We present here a comparative molecular dynamics study of unmodified and phosphorylated PLB immersed in a phospholipid membrane. The study has been performed under different ionic strength conditions, using the NMR structures of two PLB variants determined in mixed organic solvent and dodecylphosphocholine micelles. The simulations indicate that all PLB forms studied display a highly dynamic behavior of the N‐terminal cytoplasmic moiety, with a decrease of its helical content in the phosphorylated forms. The cytoplasmic domain undergoes large collective motions sampling conformations parallel as well as perpendicular to the membrane surface in all the simulations. The transmembrane domain retains a tightly folded helical conformation with a small tilt with respect to the membrane plane probably induced by the presence of Asn30 and Asn34 within the hydrophobic environment. Furthermore, the phosphoric group on Ser16 establishes transient electrostatic interactions with the phospholipid heads. We propose a model in which phosphorylation diminishes the probability of interactions of PLB with residues near Lys400 in the SERCA pump, thus relieving itsinhibition. Proteins 2007 © 2006 Wiley‐Liss, Inc.