Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization.
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4527731?pdf=render |
| _version_ | 1811273311569575936 |
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| author | Alicia Guasch Álvaro Aranguren-Ibáñez Rosa Pérez-Luque David Aparicio Sergio Martínez-Høyer M Carmen Mulero Eva Serrano-Candelas Mercè Pérez-Riba Ignacio Fita |
| author_facet | Alicia Guasch Álvaro Aranguren-Ibáñez Rosa Pérez-Luque David Aparicio Sergio Martínez-Høyer M Carmen Mulero Eva Serrano-Candelas Mercè Pérez-Riba Ignacio Fita |
| author_sort | Alicia Guasch |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T22:56:51Z |
| format | Article |
| id | doaj.art-64e2ba1d62a94d6d85dbf07c266b1bd4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T22:56:51Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-64e2ba1d62a94d6d85dbf07c266b1bd42022-12-22T03:13:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013456910.1371/journal.pone.0134569Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization.Alicia GuaschÁlvaro Aranguren-IbáñezRosa Pérez-LuqueDavid AparicioSergio Martínez-HøyerM Carmen MuleroEva Serrano-CandelasMercè Pérez-RibaIgnacio FitaA 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.http://europepmc.org/articles/PMC4527731?pdf=render |
| spellingShingle | Alicia Guasch Álvaro Aranguren-Ibáñez Rosa Pérez-Luque David Aparicio Sergio Martínez-Høyer M Carmen Mulero Eva Serrano-Candelas Mercè Pérez-Riba Ignacio Fita Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization. PLoS ONE |
| title | Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization. |
| title_full | Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization. |
| title_fullStr | Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization. |
| title_full_unstemmed | Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization. |
| title_short | Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization. |
| title_sort | calcineurin undergoes a conformational switch evoked via peptidyl prolyl isomerization |
| url | http://europepmc.org/articles/PMC4527731?pdf=render |
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