Cargando…

The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes

Hormone receptors require participation of the chaperones Hsp40/Hsp70 to form client-transfer complexes with Hsp90/Hop. Interaction with the co-chaperone p23 releases Hop and Hsp70, and the immunophilin FKBP52 mediates transfer of the Hsp90-receptor complex to the nucleus. Inhibition of glucocortico...

Descripción completa

Detalles Bibliográficos
Autores principales: Ebong, Ima-obong, Beilsten-Edmands, Victoria, Patel, Nisha A, Morgner, Nina, Robinson, Carol V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849472/
https://www.ncbi.nlm.nih.gov/pubmed/27462449
http://dx.doi.org/10.1038/celldisc.2016.2
_version_ 1782429545566044160
author Ebong, Ima-obong
Beilsten-Edmands, Victoria
Patel, Nisha A
Morgner, Nina
Robinson, Carol V
author_facet Ebong, Ima-obong
Beilsten-Edmands, Victoria
Patel, Nisha A
Morgner, Nina
Robinson, Carol V
author_sort Ebong, Ima-obong
collection PubMed
description Hormone receptors require participation of the chaperones Hsp40/Hsp70 to form client-transfer complexes with Hsp90/Hop. Interaction with the co-chaperone p23 releases Hop and Hsp70, and the immunophilin FKBP52 mediates transfer of the Hsp90-receptor complex to the nucleus. Inhibition of glucocorticoid receptor (GR) transport by FKBP51, but not by FKBP52, has been observed at the cellular level, but the subunit composition of the intermediates involved has not been deduced. Here we use mass spectrometry to show that FKBP51/52 form analogous complexes with GR/Hsp90/Hop/Hsp70/ATP, but differences emerge upon addition of p23 to client-transfer complexes. When FKBP51 is present, a stable intermediate is formed (FKBP51)(1)(GR)(1)(Hsp90)(2)(p23)(2) by expulsion of Hsp70 and Hop. By contrast, in the presence of FKBP52, ejection of p23 also takes place to form the nuclear transfer complex (FKBP52)(1)(GR)(1)(Hsp90)(2). Our results are therefore consistent with pathways in which FKBP51/52 are interchangeable during the early assembly reactions. Following interaction with p23, however, the pathways diverge with FKBP51 sequestering GR in a stable intermediate complex with p23. By contrast, binding of FKBP52 occurs almost concomitantly with release of p23 to form a highly dynamic transfer complex, primed for interaction with the dynactin transport machinery.
format Online
Article
Text
id pubmed-4849472
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-48494722016-07-26 The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes Ebong, Ima-obong Beilsten-Edmands, Victoria Patel, Nisha A Morgner, Nina Robinson, Carol V Cell Discov Article Hormone receptors require participation of the chaperones Hsp40/Hsp70 to form client-transfer complexes with Hsp90/Hop. Interaction with the co-chaperone p23 releases Hop and Hsp70, and the immunophilin FKBP52 mediates transfer of the Hsp90-receptor complex to the nucleus. Inhibition of glucocorticoid receptor (GR) transport by FKBP51, but not by FKBP52, has been observed at the cellular level, but the subunit composition of the intermediates involved has not been deduced. Here we use mass spectrometry to show that FKBP51/52 form analogous complexes with GR/Hsp90/Hop/Hsp70/ATP, but differences emerge upon addition of p23 to client-transfer complexes. When FKBP51 is present, a stable intermediate is formed (FKBP51)(1)(GR)(1)(Hsp90)(2)(p23)(2) by expulsion of Hsp70 and Hop. By contrast, in the presence of FKBP52, ejection of p23 also takes place to form the nuclear transfer complex (FKBP52)(1)(GR)(1)(Hsp90)(2). Our results are therefore consistent with pathways in which FKBP51/52 are interchangeable during the early assembly reactions. Following interaction with p23, however, the pathways diverge with FKBP51 sequestering GR in a stable intermediate complex with p23. By contrast, binding of FKBP52 occurs almost concomitantly with release of p23 to form a highly dynamic transfer complex, primed for interaction with the dynactin transport machinery. Nature Publishing Group 2016-04-05 /pmc/articles/PMC4849472/ /pubmed/27462449 http://dx.doi.org/10.1038/celldisc.2016.2 Text en Copyright © 2016 SIBS, CAS http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ebong, Ima-obong
Beilsten-Edmands, Victoria
Patel, Nisha A
Morgner, Nina
Robinson, Carol V
The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes
title The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes
title_full The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes
title_fullStr The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes
title_full_unstemmed The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes
title_short The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes
title_sort interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of hsp90 glucocorticoid receptor complexes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849472/
https://www.ncbi.nlm.nih.gov/pubmed/27462449
http://dx.doi.org/10.1038/celldisc.2016.2
work_keys_str_mv AT ebongimaobong theinterchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes
AT beilstenedmandsvictoria theinterchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes
AT patelnishaa theinterchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes
AT morgnernina theinterchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes
AT robinsoncarolv theinterchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes
AT ebongimaobong interchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes
AT beilstenedmandsvictoria interchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes
AT patelnishaa interchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes
AT morgnernina interchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes
AT robinsoncarolv interchangeofimmunophilinsleadstoparallelpathwaysanddifferentintermediatesintheassemblyofhsp90glucocorticoidreceptorcomplexes