5C1V

CRYSTAL STRUCTURE ANALYSIS OF CATALYTIC SUBUNIT OF HUMAN CALCINEURIN

Summary for 5C1V

• Entry DOI: 10.2210/pdb5c1v/pdb
• Descriptor: Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform, FE (III) ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: 4-layer sandwich, serine/threonine phosphatase, calcium binding, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane : Q08209
• Total number of polymer chains: 2
• Total formula weight: 79979.18

Authors

Guasch, A.,Fita, I.,Perez-Luque, R.,Aparicio, D.,Aranguren-Ibanez, A.,Perez-Riba, M. (deposition date: 2015-06-15, release date: 2016-02-03, Last modification date: 2024-01-10)

Primary citation

Guasch, A.,Aranguren-Ibanez, A.,Perez-Luque, R.,Aparicio, D.,Martinez-Hyer, S.,Mulero, M.C.,Serrano-Candelas, E.,Perez-Riba, M.,Fita, I.
Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization.
Plos One, 10:e0134569-e0134569, 2015

PubMed 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.

PubMed: 26248042
DOI: 10.1371/journal.pone.0134569

Experimental method

X-RAY DIFFRACTION (3.35 Å)