Non-inositol 1,4,5-trisphosphate (IP) receptor IP-binding proteins.

Conventionally, myo-D-inositol 1, 4,5-trisphosphate (IP) is thought to exert its second messenger effects through the gating of IPR Ca release channels, located in Ca-storage organelles like the endoplasmic reticulum. However, there is considerable indirect evidence to support the concept that IP might interact with other, non-IPR proteins within cells. To explore this possibility further, the Protein Data Bank was searched using the term "IP3". This resulted in the retrieval of 203 protein structures, the majority of which were members of the IPR/ryanodine receptor superfamily of channels. Only 49 of these structures were complexed with IP. These were inspected for their ability to interact with the carbon-1 phosphate of IP, since this is the least accessible phosphate group of its precursor, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P). This reduced the number of structures retrieved to 35, of which 9 were IPRs. The remaining 26 structures represent a diverse range of proteins, including inositol-lipid metabolizing enzymes, signal transducers, PH domain containing proteins, cytoskeletal anchor proteins, the TRPV4 ion channel, a retroviral Gag protein and fibroblast growth factor 2. Such proteins may impact on IP signalling and its effects on cell-biology. This represents an area open for exploration in the field of IP signalling.