FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin.
The protein factor Glomulin (Glmn) is a regulator of the SCF (Skp1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. Mutations of Glmn lead to glomuvenous malformations. Glmn has been reported to be associated with FK506-binding proteins (FKBP). Here we present in vitro binding analyses of th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0221926 |
| _version_ | 1818986628577755136 |
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| author | Andreas Hähle Thomas M Geiger Stephanie Merz Christian Meyners Mao Tianqi Jürgen Kolos Felix Hausch |
| author_facet | Andreas Hähle Thomas M Geiger Stephanie Merz Christian Meyners Mao Tianqi Jürgen Kolos Felix Hausch |
| author_sort | Andreas Hähle |
| collection | DOAJ |
| description | The protein factor Glomulin (Glmn) is a regulator of the SCF (Skp1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. Mutations of Glmn lead to glomuvenous malformations. Glmn has been reported to be associated with FK506-binding proteins (FKBP). Here we present in vitro binding analyses of the FKBP-Glmn interaction. Interestingly, the previously described interaction of Glmn and FKBP12 was found to be comparatively weak. Instead, the closely related FKBP12.6 and FKBP51 emerged as novel binding partners. We show different binding affinities of full length and truncated FKBP51 and FKBP52 mutants. Using FKBP51 as a model system, we show that two amino acids lining the FK506-binding site are essential for binding Glmn and that the FKBP51-Glmn interaction is blocked by FKBP ligands. This data suggest FKBP inhibition as a pharmacological approach to regulate Glmn and Glmn-controlled processes. |
| first_indexed | 2024-12-20T18:53:49Z |
| format | Article |
| id | doaj.art-eb801d8576204153a43254d72f82e7ae |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T18:53:49Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-eb801d8576204153a43254d72f82e7ae2022-12-21T19:29:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01149e022192610.1371/journal.pone.0221926FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin.Andreas HähleThomas M GeigerStephanie MerzChristian MeynersMao TianqiJürgen KolosFelix HauschThe protein factor Glomulin (Glmn) is a regulator of the SCF (Skp1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. Mutations of Glmn lead to glomuvenous malformations. Glmn has been reported to be associated with FK506-binding proteins (FKBP). Here we present in vitro binding analyses of the FKBP-Glmn interaction. Interestingly, the previously described interaction of Glmn and FKBP12 was found to be comparatively weak. Instead, the closely related FKBP12.6 and FKBP51 emerged as novel binding partners. We show different binding affinities of full length and truncated FKBP51 and FKBP52 mutants. Using FKBP51 as a model system, we show that two amino acids lining the FK506-binding site are essential for binding Glmn and that the FKBP51-Glmn interaction is blocked by FKBP ligands. This data suggest FKBP inhibition as a pharmacological approach to regulate Glmn and Glmn-controlled processes.https://doi.org/10.1371/journal.pone.0221926 |
| spellingShingle | Andreas Hähle Thomas M Geiger Stephanie Merz Christian Meyners Mao Tianqi Jürgen Kolos Felix Hausch FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin. PLoS ONE |
| title | FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin. |
| title_full | FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin. |
| title_fullStr | FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin. |
| title_full_unstemmed | FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin. |
| title_short | FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin. |
| title_sort | fkbp51 and fkbp12 6 novel and tight interactors of glomulin |
| url | https://doi.org/10.1371/journal.pone.0221926 |
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