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PDBsum entry 3ewv
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Calcium binding protein
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PDB id
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3ewv
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References listed in PDB file
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Key reference
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Title
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Structural insights into the mechanism of calmodulin binding to death receptors.
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Authors
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P.Cao,
W.Zhang,
W.Gui,
Y.Dong,
T.Jiang,
Y.Gong.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2014,
70,
1604-1613.
[DOI no: ]
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PubMed id
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Abstract
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The death receptors Fas, p75(NTR) and DR6 are key components of extrinsically
activated apoptosis. Characterization of how they interact with the adaptors is
crucial in order to unravel the signalling mechanisms. However, the exact
conformation that their intracellular death domain adopts upon binding
downstream partners remains unclear. One model suggests that it adopts a typical
compact fold, whilst a second model proposed an open conformation. Calmodulin
(CaM), a major calcium sensor, has previously been reported to be one of the Fas
adaptors that modulate apoptosis. This work reports that CaM also binds directly
to the death domains of p75(NTR) and DR6, indicating that it serves as a common
modulator of the death receptors. Two crystal structures of CaM in complexes
with the corresponding binding regions of Fas and p75(NTR) are also reported.
Interestingly, the precise CaM-binding sites were mapped to different regions:
helix 1 in Fas and helix 5 in p75(NTR) and DR6. A novel 1-11 motif for CaM
binding was observed in p75(NTR). Modelling the complexes of CaM with
full-length receptors reveals that the opening of the death domains would be
essential in order to expose their binding sites for CaM. These results may
facilitate understanding of the diverse functional repertoire of death receptors
and CaM and provide further insights necessary for the design of potential
therapeutic peptide agents.
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