A Novel Calmodulin-Ca2+ Target Recognition Activates the Bcl-2 Regulator FKBP38

Edlich, Frank; Maestre-Martínez, Mitcheell; Jarczowski, Franziska; Weiwad, Matthias; Moutty, Marie-Christine; Malešević, Miroslav; Jahreis, Günther; Fischer, Gunter; Lücke, Christian

doi:10.1074/jbc.m705061200

Cited by 32 publications

(29 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Detailed structural insight into the binding process between both complex partners provides the molecular basis of FKBP38-mediated Bcl-2 regulation in human cells. The results presented here show that the formation of the FKBP38⅐Bcl-2 complex could be affected by the presence of other electrostatic factors such as Ca 2ϩ and thus provide a rationale as to why high Ca 2ϩ concentrations reduce the regulatory interaction between FKBP38 and Bcl-2 despite the requirement of CaM/Ca 2ϩ in cells (3,13).…”

Section: Bcl-2 Peptide Library Assay Reveals Specific Fkbp38-bindingmentioning

confidence: 79%

“…Inside the cell, this interaction is apparently dependent on prior formation of the FKBP38⅐CaM⅐Ca 2ϩ complex (9,13). In this study, we identified the contact regions between the FKBP38 catalytic domain (FKBP38(35-153)) and the cytosolic segment of Bcl-2 (Bcl-2(1-211)).…”

Section: Bcl-2 Peptide Library Assay Reveals Specific Fkbp38-bindingmentioning

confidence: 99%

“…Epitope-The interplay between Bcl-2 and its regulator FKBP38 has been shown in a number of experimental settings (3,8,9,13,17). Inside the cell, this interaction is apparently dependent on prior formation of the FKBP38⅐CaM⅐Ca 2ϩ complex (9,13).…”

Section: Bcl-2 Peptide Library Assay Reveals Specific Fkbp38-bindingmentioning

confidence: 99%

“…a subunit of the hepatitis C virus replicase) (10), HIF1 prolyl 4-hydroxylase (11,12), Hsp90 (13), and mTOR (14) and its activator Rheb (15) have been shown. The binding of FKBP38 to calmodulin for PPIase activation (9,13,16) and to Bcl-2 has been implicated in apoptosis regulation (8,9,13,(17)(18)(19).…”

mentioning

confidence: 99%

“…Kang et al (17) suggested that a long flexible loop between the BH4 and BH3 domains of Bcl-2 mediates the binding to FKBP38 and that this protein/protein interaction can prevent phosphorylation of the flexible loop, which would lead to apoptosis as a result of Bcl-2 degradation by caspase-3. Edlich et al (9,13) identified a CaM-dependent binding interaction between the FKBP38 catalytic domain and Bcl-2, which gave rise to a pro-apoptotic effect in cell experiments. Also on the basis of cell experiments, Choi et al (19) reported that the PPIase and TPR domains of FKBP38 bind to Bcl-2 by affecting primarily its flexible loop between the BH4 and BH3 domains.…”

mentioning

confidence: 99%

See 4 more Smart Citations

The FKBP38 Catalytic Domain Binds to Bcl-2 via a Charge-sensitive Loop

Haupt

Jahreis

Linnert

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Bcl-2 Peptide Library Assay Reveals Specific Fkbp38-bindingmentioning

confidence: 79%

Section: Bcl-2 Peptide Library Assay Reveals Specific Fkbp38-bindingmentioning

confidence: 99%

Section: Bcl-2 Peptide Library Assay Reveals Specific Fkbp38-bindingmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

The FKBP38 Catalytic Domain Binds to Bcl-2 via a Charge-sensitive Loop

Haupt

Jahreis

Linnert

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

A twist in the ABC: regulation of ABC transporter trafficking and transport by FK506‐binding proteins

Geisler

Hegedüs

2020

FEBS Letters

View full text Add to dashboard Cite

Post‐transcriptional regulation of ATP‐binding cassette (ABC) proteins has been so far shown to encompass protein phosphorylation, maturation, and ubiquitination. Yet, recent accumulating evidence implicates FK506‐binding proteins (FKBPs), a type of peptidylprolyl cis–trans isomerase (PPIase) proteins, in ABC transporter regulation. In this perspective article, we summarize current knowledge on ABC transporter regulation by FKBPs, which seems to be conserved over kingdoms and ABC subfamilies. We uncover striking functional similarities but also differences between regulatory FKBP‐ABC modules in plants and mammals. We dissect a PPIase‐ and HSP90‐dependent and independent impact of FKBPs on ABC biogenesis and transport activity. We propose and discuss a putative new mode of transient ABC transporter regulation by cis–trans isomerization of X‐prolyl bonds.

show abstract

A charge-sensitive loop in the FKBP38 catalytic domain modulates Bcl-2 binding

et al. 2010

Self Cite

View full text Add to dashboard Cite

The Bcl-2 inhibitor FKBP38 is regulated by the Ca(2+)-sensor calmodulin (CaM). Here we show a hitherto unknown low-affinity cation-binding site in the FKBP domain of FKBP38, which may afford an additional level of regulation based on electrostatic interactions. Fluorescence titration experiments indicate that in particular the physiologically relevant Ca(2+) ion binds to this site. NMR-based chemical shift perturbation data locate this cation-interaction site within the β5-α1 loop (Leu90-Ile96) of the FKBP domain, which contains the acidic Asp92 and Asp94 side-chains. Binding constants were subsequently determined for K(+), Mg(2+), Ca(2+), and La(3+), indicating that the net charge and the radius of the ion influences the binding interaction. X-ray diffraction data furthermore show that the conformation of the β5-α1 loop is influenced by the presence of a positively charged guanidinium group belonging to a neighboring FKBP38 molecule in the crystal lattice. The position of the cation-binding site has been further elucidated based on pseudocontact shift data obtained by NMR via titration with Tb(3+). Elimination of the Ca(2+)-binding capacity by substitution of the respective aspartate residues in a D92N/D94N double-substituted variant reduces the Bcl-2 affinity of the FKBP38(35-153)/CaM complex to the same degree as the presence of Ca(2+) in the wild-type protein. Hence, this charge-sensitive site in the FKBP domain participates in the regulation of FKBP38 function by enabling electrostatic interactions with ligand proteins and/or salt ions such as Ca(2+).

show abstract

A Novel Calmodulin-Ca2+ Target Recognition Activates the Bcl-2 Regulator FKBP38

Cited by 32 publications

References 35 publications

The FKBP38 Catalytic Domain Binds to Bcl-2 via a Charge-sensitive Loop

The FKBP38 Catalytic Domain Binds to Bcl-2 via a Charge-sensitive Loop

A twist in the ABC: regulation of ABC transporter trafficking and transport by FK506‐binding proteins

A charge-sensitive loop in the FKBP38 catalytic domain modulates Bcl-2 binding

Contact Info

Product

Resources

About