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Title: Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization.
Author: Guasch, Alicia
Aranguren Ibáñez, Álvaro
Pérez Luque, Rosa
Aparicio, David
Martínez Høyer, Sergio
Mulero, M.Carmen
Serrano Candelas, Eva
Pérez Riba, Mercè
Fita Rodríguez, Ignasi
Keywords: Estructura cristal·lina (Sòlids)
Síntesi de pèptids
Interaccions dels medicaments
Layer structure (Solids)
Peptide synthesis
Drug interactions
Issue Date: 6-Aug-2015
Publisher: Public Library of Science (PLoS)
Abstract: A limited repertoire of PPP family of serine/threonine phosphatases with a highly conserved catalytic domain acts on thousands of protein targets to orchestrate myriad central biological roles. A major structural reorganization of human calcineurin, a ubiquitous Ser/Thr PPP regulated by calcium and calmodulin and targeted by immunosuppressant drugs cyclosporin A and FK506, is unveiled here. The new conformation involves trans- to cis- isomerization of proline in the SAPNY sequence, highly conserved across PPPs, and remodels the main regulatory site where NFATc transcription factors bind. Transitions between cis- and trans- conformations may involve peptidyl prolyl isomerases such as cyclophilin A and FKBP12, which are known to physically interact with and modulate calcineurin even in the absence of immunosuppressant drugs. Alternative conformations in PPPs provide a new perspective on interactions with substrates and other protein partners and may foster development of more specific inhibitors as drug candidates.
Note: Reproducció del document publicat a:
It is part of: PLoS One, 2015, vol. 10, num. 8, p. e0134569-e0134569
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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