Structural highlights
Function[PP2BA_HUMAN] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.[1] [2] Publication Abstract from PubMedA 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. Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization.,Guasch A, Aranguren-Ibanez A, Perez-Luque R, Aparicio D, Martinez-Hoyer S, Mulero MC, Serrano-Candelas E, Perez-Riba M, Fita I PLoS One. 2015 Aug 6;10(8):e0134569. doi: 10.1371/journal.pone.0134569., eCollection 2015. PMID:26248042[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
This page was last modified 15:41, 3 February 2016.