A novel calmodulin-Ca2+ target recognition activates the Bcl-2 regulator FKBP38 - PubMed (original) (raw)

. 2007 Dec 14;282(50):36496-504.

doi: 10.1074/jbc.M705061200. Epub 2007 Oct 17.

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A novel calmodulin-Ca2+ target recognition activates the Bcl-2 regulator FKBP38

Frank Edlich et al. J Biol Chem. 2007.

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Abstract

The FK506-binding protein 38 (FKBP38) affects neuronal apoptosis control by suppressing the anti-apoptotic function of Bcl-2. The direct interaction between FKBP38 and Bcl-2, however, requires a prior activation of FKBP38 by the Ca2+ sensor calmodulin (CaM). Here we demonstrate for the first time that the formation of a complex between FKBP38 and CaM-Ca2+ involves two separate interaction sites, thus revealing a novel scenario of target protein regulation by CaM-Ca2+. The C-terminal FKBP38 residues Ser290-Asn313 bind to the target protein-binding cleft of the Ca2+-coordinated C-terminal CaM domain, thereby enabling the N-terminal CaM domain to interact with the catalytic domain of FKBP38 in a Ca2+-independent manner. Only the latter interaction between the catalytic FKBP38 domain and the N-terminal CaM domain activates FKBP38 and, as a consequence, also regulates Bcl-2.

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