Stochastic machines as a colocalization mechanism for scaffold protein function

FEBS Lett. 2013 Jun 5;587(11):1587-91. doi: 10.1016/j.febslet.2013.04.006. Epub 2013 Apr 18.


The axis inhibition (Axin) scaffold protein colocalizes β-catenin, casein kinase Iα, and glycogen synthetase kinase 3β by their binding to Axin's long intrinsically disordered region, thereby yielding structured domains with flexible linkers. This complex leads to the phosphorylation of β-catenin, marking it for destruction. Fusing proteins with flexible linkers vastly accelerates chemical interactions between them by their colocalization. Here we propose that the complex works by random movements of a "stochastic machine," not by coordinated conformational changes. This non-covalent, modular assembly process allows the various molecular machine components to be used in multiple processes.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Axin Signaling Complex / chemistry*
  • Axin Signaling Complex / physiology
  • Casein Kinase I / chemistry
  • Humans
  • Models, Molecular*
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Protein Structure, Quaternary
  • Protein Transport
  • Proteolysis
  • Stochastic Processes
  • Wnt Signaling Pathway
  • beta Catenin / chemistry


  • Axin Signaling Complex
  • beta Catenin
  • Casein Kinase I