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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2019-09, Vol.14 (9), p.e0221926-e0221926
Main Authors: Hähle, Andreas, Geiger, Thomas M, Merz, Stephanie, Meyners, Christian, Tianqi, Mao, Kolos, Jürgen, Hausch, Felix
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Amino acids
Apoptosis
Binding proteins
Binding sites
Biochemistry
Biology and Life Sciences
Catalytic Domain
F-box protein
Gene expression
Ligands
Ligases
Metabolism
Mutants
Mutation
Novels
Organic chemistry
Physical Sciences
Protein Binding
Proteins
Research and Analysis Methods
Tacrolimus
Tacrolimus Binding Proteins - chemistry
Tacrolimus Binding Proteins - genetics
Tacrolimus Binding Proteins - metabolism
Tacrolimus-binding protein
Ubiquitin
Ubiquitin-protein ligase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0221926