Protein nanoparticles engineered to sense kinase activity in MRI

J Am Chem Soc. 2009 Feb 25;131(7):2484-6. doi: 10.1021/ja8086938.

Abstract

We introduce a family of protein nanoparticles capable of sensing analytes in conjunction with magnetic resonance imaging (MRI). The new sensors are derived from the iron storage protein ferritin (Ft); they are designed and optimized using facile protein engineering methods, and self-assembled in cells harboring specific combinations of DNA coding sequences. As illustration, we show that suitably constructed Ft-based sensors can report activity of the important neural signaling enzyme protein kinase A (PKA). Phosphorylation of the engineered Ft-based nanoparticles by PKA promotes clustering and changes in T(2)-weighted MRI signal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques / methods
  • CREB-Binding Protein / chemistry
  • CREB-Binding Protein / metabolism
  • Cyclic AMP Response Element-Binding Protein / chemistry
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / analysis*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Ferritins / chemistry*
  • Ferritins / metabolism
  • Magnetic Resonance Imaging / methods*
  • Nanoparticles / chemistry*
  • Phosphorylation
  • Protein Structure, Tertiary

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Ferritins
  • CREB-Binding Protein
  • Cyclic AMP-Dependent Protein Kinases