Characterization of the binding sites for the interactions between FKBP12 and intracellular calcium release channels.
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Wen H, Kang S, Song Y, Song Y, Yang HJ, Kim MH, Park S
Characterization of the binding sites for the interactions between FKBP12 and intracellular calcium release channels.
Arch Biochem Biophys. 2012 Jan 1;517(1):37-42. doi: 10.1016/j.abb.2011.11.004. Epub 2011 Nov 11.
- PubMed ID
- 22100703 [ View in PubMed]
- Abstract
FKBP12, an FK506 binding protein, interacts with type 1 ryanodine receptor (RyR1) and modulates its calcium channel activity. However, there are many opposing reports of FKBP12's interaction with other related calcium channels, such as type 1 IP(3) receptor and type 3 ryanodine receptor (IP(3)R1 and RyR3). In addition, the involvement of the prolyl-dipeptide motif in the calcium channels and the corresponding binding residues in FKBP12 remain controversial. Through pulldown assays with recombinant proteins, we provide biochemical evidence of the interaction between FKBP12 and RyR1, RyR3 and IP(3)R1. Using NMR chemical shift mapping, we show that the important binding residues in FKBP12 are located in its hydrophobic FK506 binding region. Consistently, we demonstrate that FK506 can competitively inhibit the interaction between FKBP12 and the dipeptide motifs of the calcium channels. We believe our results shed lights on the binding mechanism of calcium channel-FKBP12 interaction.