The FKBP38 Catalytic Domain Binds to Bcl-2 via a Charge-sensitive Loop
| Autor: | Katja Haupt, Frank Edlich, Miriam Linnert, Mitcheell Maestre-Martínez, Arndt Pechstein, Christian Lücke, Miroslav Malesevic, Günther Jahreis |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Biochemistry Protein Structure Secondary Tacrolimus Binding Proteins Epitopes Protein structure Peptide Library Humans Peptide library Site-directed mutagenesis Molecular Biology Nuclear Magnetic Resonance Biomolecular biology Chemistry Active site Cell Biology Nuclear magnetic resonance spectroscopy Protein tertiary structure Protein Structure Tertiary Heteronuclear molecule Proto-Oncogene Proteins c-bcl-2 Protein Structure and Folding biology.protein Biophysics Calcium Hydrophobic and Hydrophilic Interactions Binding domain |
| Popis: | FKBP38 is a regulator of the prosurvival protein Bcl-2, but in the absence of detailed structural insights, the molecular mechanism of the underlying interaction has remained unknown. Here, we report the contact regions between Bcl-2 and the catalytic domain of FKBP38 derived by heteronuclear NMR spectroscopy. The data reveal that a previously identified charge-sensitive loop near the putative active site of FKBP38 is mainly responsible for Bcl-2 binding. The corresponding binding epitope of Bcl-2 could be identified via a peptide library-based membrane assay. Site-directed mutagenesis of the key residues verified the contact sites of this electrostatic protein/protein interaction. The derived structure model of the complex between Bcl-2 and the FKBP38 catalytic domain features both electrostatic and hydrophobic intermolecular contacts and provides a rationale for the regulation of the FKBP38/Bcl-2 interaction by Ca(2+). |
| Databáze: | OpenAIRE |
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