科研之友
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摘要
Calcium-binding protein 1 (CaBP1), a neuron-specific member of the calmodulin (CaM) superfamily, regulates the Ca2+-dependent activity of inositol 1,4,5-triphosphate receptors (InsP3Rs) and various voltage-gated Ca2+ channels. Here, we present the NMR structure of full-length CaBP1 with Ca2+ bound at the first, third, and fourth EF-hands. A total of 1250 nuclear Overhauser effect distance measurements and 70 residual dipolar coupling restraints define the overall main chain structure with a root-mean-squared deviation of 0.54 angstrom (N-domain) and 0.48 angstrom (C-domain). The first 18 residues from the N-terminus in CaBP1 (located upstream of the first EF-hand) are structurally disordered and solvent exposed. The Ca2+-saturated CaBP1 structure contains two independent domains separated by a flexible central linker similar to that in calmodulin and troponin C. The N-domain structure of CaBP1 contains two EF-hands (EF1 and EF2), both in a closed conformation [interhelical angles = 129 degrees (EF1) and 142 degrees (EF2)]. The C-domain contains EF3 and EF4 in the familiar Ca2+-bound open conformation [interhelical angles = 105 degrees (EF3) and 91 degrees (EF4)]. Surprisingly, the N-domain adopts the same closed conformation in the presence or absence of Ca2+ bound at EF1. The Ca2+-bound closed conformation of EF1 is reminiscent of Ca2+-bound EF-hands in a closed conformation found in cardiac troponin C and calpain. We propose that the Ca2+-bound closed conformation of EF1 in CaBP1 might undergo an induced-fit opening only in the presence of a specific target protein, and thus may help explain the highly specialized target binding by CaBP1.
- 出版日期2011-8
