Biophysical Reviews

, 3:143 | Cite as

Structural gymnastics of multifunctional metamorphic proteins

  • Sophia C. Goodchild
  • Paul M. G. Curmi
  • Louise J. Brown


The classic structure–function paradigm holds that a protein exhibits a single well-defined native state that gives rise to its biological function. Nonetheless, over the past few decades, numerous examples of proteins exhibiting biological function arising from multiple structural states of varying disorder have been identified. Most recently, several examples of ‘metamorphic proteins’, able to interconvert between vastly different native-like topologies under physiological conditions, have been characterised with multiple functions. In this review, we look at the concept of protein metamorphosis in relation to the current understanding of the protein structure–function landscape. Although structural dynamism observed for metamorphic proteins provides a novel source of functional versatility, the dynamic nature of the metamorphic proteins generally makes them difficult to identify and probe using conventional protein structure determination methods. However, as the existence of metamorphic proteins has now been established and techniques enabling the analysis of multiple protein conformers are improving, it is likely that this class will continue to grow in number.


Metamorphic proteins Lymphotactin Mad2 CLIC1 



Chloride intracellular channel


Electron paramagnetic resonance


Fluorescence resonance energy transfer


Intrinsically disordered proteins




Mitotic arrest deficient 2


Molten globule


Serpin reactive centre loop


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Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer 2011

Authors and Affiliations

  • Sophia C. Goodchild
    • 1
  • Paul M. G. Curmi
    • 2
    • 3
  • Louise J. Brown
    • 1
  1. 1.Department of Chemistry and Biomolecular SciencesMacquarie UniversitySydneyAustralia
  2. 2.School of PhysicsUniversity of New South WalesSydneyAustralia
  3. 3.Centre for Applied Medical ResearchSt Vincent’s HospitalSydneyAustralia

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