Structural dynamics of muscle protein phosphorylation

Brett A. Colson, Simon J. Gruber, David D. Thomas

Research output: Contribution to journalReview article

10 Scopus citations

Abstract

We have used site-directed spectroscopic probes to detect structural changes, motions, and interactions due to phosphorylation of proteins involved in the regulation of muscle contraction and relaxation. Protein crystal structures provide static snapshots that provide clues to the conformations that are sampled dynamically by proteins in the cellular environment. Our site-directed spectroscopic experiments, combined with computational simulations, extend these studies into functional assemblies in solution, and reveal details of protein regions that are too dynamic or disordered for crystallographic approaches. Here, we discuss phosphorylation-mediated structural transitions in the smooth muscle myosin regulatory light chain, the striated muscle accessory protein myosin binding protein-C, and the cardiac membrane Ca2+ pump modulator phospholamban. In each of these systems, phosphorylation near the N terminus of the regulatory protein relieves an inhibitory interaction between the phosphoprotein and its regulatory target. Several additional unifying themes emerge from our studies: (a) The effect of phosphorylation is not to change the affinity of the phosphoprotein for its regulated binding partner, but to change the structure of the bound complex without dissociation. (b) Phosphorylation induces transitions between order and dynamic disorder. (c) Structural states are only loosely coupled to phosphorylation; i.e., complete phosphorylation induces dramatic functional effects with only a partial shift in the equilibrium between ordered and disordered structural states. These studies, which offer atomic-resolution insight into the structural and functional dynamics of these phosphoproteins, were inspired in part by the ground-breaking work in this field by Michael and Kate Barany.

Original languageEnglish (US)
Pages (from-to)419-429
Number of pages11
JournalJournal of Muscle Research and Cell Motility
Volume33
Issue number6
DOIs
StatePublished - Aug 29 2012
Externally publishedYes

Keywords

  • Muscle regulation
  • Myosin binding protein-C
  • Phospholamban
  • Regulatory light chain
  • Spectroscopy
  • Structural dynamics

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cell Biology

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