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Updated: Apr 5, 2026

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
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Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization

Alicia Guasch1, Álvaro Aranguren-Ibáñez2, Rosa Pérez-Luque1

  • 1Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Parc Científic, Baldiri Reixac 10, 08028, Barcelona, Spain.

Plos One
|August 7, 2015
PubMed

Insights

Structural changes in calcineurin, a key phosphatase, reveal new insights into its regulation. This discovery may lead to more targeted drug development for various conditions.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • The PPP family of serine/threonine phosphatases plays crucial roles in cellular processes.
  • Calcineurin, a calcium/calmodulin-regulated PPP, is a target for immunosuppressive drugs like cyclosporin A and FK506.

Purpose of the Study:

  • To elucidate the structural reorganization of human calcineurin.
  • To understand the mechanism of calcineurin regulation and its interaction with NFATc transcription factors.

Main Methods:

  • X-ray crystallography or Cryo-EM to determine the structure of calcineurin.
  • Biochemical assays to study the functional implications of the observed structural changes.

Main Results:

  • A novel conformation of calcineurin involving trans- to cis-isomerization of proline in the conserved SAPNY motif was identified.
  • This structural change remodels the regulatory site for NFATc transcription factors.
  • Peptidyl prolyl isomerases like cyclophilin A and FKBP12 may mediate transitions between calcineurin conformations.

Conclusions:

  • Alternative conformations of PPPs, including calcineurin, offer new perspectives on protein-protein interactions.
  • Understanding these conformational dynamics can aid in developing more specific inhibitors for therapeutic applications.

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