Dynamic allostery: linkers are not merely flexible

Structure. 2011 Jul 13;19(7):907-17. doi: 10.1016/j.str.2011.06.002.


Most proteins consist of multiple domains. How do linkers efficiently transfer information between sites that are on different domains to activate the protein? Mere flexibility only implies that the conformations would be sampled. For fast timescales between triggering events and cellular response, which often involves large conformational change, flexibility on its own may not constitute a good solution. We posit that successive conformational states along major allosteric propagation pathways are pre-encoded in linker sequences where each state is encoded by the previous one. The barriers between these states that are hierarchically populated are lower, achieving faster timescales even for large conformational changes. We further propose that evolution has optimized the linker sequences and lengths for efficiency, which explains why mutations in linkers may affect protein function and review the literature in this light.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Animals
  • Binding Sites
  • Humans
  • Models, Molecular
  • Plants
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Subunits* / chemistry
  • Protein Subunits* / metabolism
  • Proteins* / chemistry
  • Proteins* / metabolism
  • Signal Transduction*
  • Thermodynamics


  • Protein Subunits
  • Proteins