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New structural aspects of FKBP38 activation

  • Mitcheell Maestre-Martínez , Katja Haupt , Frank Edlich , Günther Jahreis , Franziska Jarczowski , Frank Erdmann , Gunter Fischer and Christian Lücke
Published/Copyright: August 13, 2010
Biological Chemistry
From the journal Volume 391 Issue 10

Abstract

The human FK506-binding protein 38 (FKBP38) regulates Bcl-2 in neuronal apoptosis. To control Bcl-2 activity, FKBP38 requires a prior interaction with the Ca2+-sensor calmodulin (CaM). The resulting FKBP38/CaM complex is unique within the FKBP family. Here, we present novel insights into the structural arrangement of this complex. Chemical shift perturbation analyses of the individual protein domains revealed two separate interaction sites between FKBP38 and CaM. On the one hand, residues Glu303, Tyr307 and Leu311, belonging to the predicted CaM-binding site at the C-terminal end of FKBP38, become embedded in the hydrophobic target protein-binding cleft of the C-terminal CaM lobe. On the other hand, in a second binding interaction, the N-terminal end of the catalytic FKBP38 domain shows surface contacts to the AB and CD loops of CaM as well as the adjacent helices. Furthermore, a Glu-rich region at the non-structured FKBP38 N-terminus features additional contacts to CaM helix A. In combination with previous results, we thus conclude that the FKBP38/CaM complex is constituted by (i) a Ca2+-dependent interaction of the CaM-binding motif at the C-terminal end of FKBP38 with the C-terminal CaM lobe and (ii) a Ca2+-independent interaction between the N-terminal CaM lobe and the N-terminal region of the catalytic FKBP38 domain.

Keywords: Bcl-2; calmodulin; chemical shift perturbation mapping; FK506 binding protein; PPIase; protein-protein interactions
Corresponding author
Received: 2010-3-25
Accepted: 2010-7-5
Published Online: 2010-08-13
Published in Print: 2010-10-01

©2010 by Walter de Gruyter Berlin New York

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https://doi.org/10.1515/bc.2010.122
Keywords for this article
Bcl-2; calmodulin; chemical shift perturbation mapping; FK506 binding protein; PPIase; protein-protein interactions

Articles in the same Issue

  1. Guest Editorial
  2. Highlight: The Biology of Aging: Mechanisms and Intervention
  3. Highlight: 61th Mosbach Colloquium of the GBM ‘The Biology of Aging: Mechanisms and Intervention’
  4. Multiplex analysis of mitochondrial DNA pathogenic and polymorphic sequence variants
  5. The hypoxia-inducible factor HIF-1 functions as both a positive and negative modulator of aging
  6. E. coli hypoxia-inducible factor ArcA mediates lifespan extension in a lipoic acid synthase mutant by suppressing acetyl-CoA synthetase
  7. Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis
  8. PROTEIN STRUCTURE AND FUNCTION
  9. New structural aspects of FKBP38 activation
  10. The neuronal proteins CIPP, Cypin and IRSp53 form a tripartite complex mediated by PDZ and SH3 domains
  11. CELL BIOLOGY AND SIGNALING
  12. Inhibition of interferon-α-induced signaling by hyperosmolarity and hydrophobic bile acids
  13. Role of the second disulfide bridge (Cys18-Cys274) in stabilizing the inactive AT1 receptor
  14. Demonstration of protein absorption in the intestinal epithelium of fish and mice by laser scanning confocal microscopy
  15. Non-genomic action of TCDD to induce inflammatory responses in HepG2 human hepatoma cells and in liver of C57BL/6J mice
  16. PROTEOLYSIS
  17. Amino acid residues modulating the activities of staphylococcal glutamyl endopeptidases
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