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FKBP51 and FKBP12.6—Novel and tight interactors of Glomulin

Geiger, Thomas M. and Hähle, Andreas and Merz, Stephanie and Meyners, Christian and Tianqi, Mao and Kolos, Jürgen and Hausch, Felix (2019):
FKBP51 and FKBP12.6—Novel and tight interactors of Glomulin.
14, In: PLOS ONE, (9), PLOS, ISSN 1932-6203, DOI: 10.1371/journal.pone.0221926,
[Online-Edition: https://doi.org/10.1371/journal.pone.0221926],
[Article]

Abstract

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.

Item Type: Article
Erschienen: 2019
Creators: Geiger, Thomas M. and Hähle, Andreas and Merz, Stephanie and Meyners, Christian and Tianqi, Mao and Kolos, Jürgen and Hausch, Felix
Title: FKBP51 and FKBP12.6—Novel and tight interactors of Glomulin
Language: English
Abstract:

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.

Journal or Publication Title: PLOS ONE
Volume: 14
Number: 9
Publisher: PLOS
Divisions: 07 Department of Chemistry
07 Department of Chemistry > Fachgebiet Biochemie
Date Deposited: 03 Nov 2019 20:57
DOI: 10.1371/journal.pone.0221926
Official URL: https://doi.org/10.1371/journal.pone.0221926
URN: urn:nbn:de:tuda-tuprints-92111
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