title: The FKBP38 catalytic domain binds to Bcl-2 via a charge-sensitive loop.
abstract: 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+).
authors.affiliation: Max Planck Research Unit for Enzymology of Protein Folding, 06120 Halle, Saale, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Haupt
authors.forename: Günther
authors.initials: G
authors.lastname: Jahreis
authors.forename: Miriam
authors.initials: M
authors.lastname: Linnert
authors.forename: Mitcheell
authors.initials: M
authors.lastname: Maestre-Martínez
authors.forename: Miroslav
authors.initials: M
authors.lastname: Malesevic
authors.forename: Arndt
authors.initials: A
authors.lastname: Pechstein
authors.forename: Frank
authors.initials: F
authors.lastname: Edlich
authors.forename: Christian
authors.initials: C
authors.lastname: Lücke
mesh_terms: D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D019151:Peptide Library; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000939:Epitopes; C471205:FKBP8 protein, human; D019151:Peptide Library; D019253:Proto-Oncogene Proteins c-bcl-2; D022021:Tacrolimus Binding Proteins; D002118:Calcium