Ca2+functions as a molecular switch that controls the mutually exclusive complex formation of pyridoxal phosphatase with CIB1 or calmodulin
Open Access
- 23 April 2020
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 594 (13), 2099-2115
- https://doi.org/10.1002/1873-3468.13795
Abstract
Pyridoxal 5′‐phosphate (PLP) is an essential cofactor for neurotransmitter metabolism. Pyridoxal phosphatase (PDXP)‐deficiency in mice increases PLP and γ‐aminobutyric acid levels in the brain, yet how PDXP is regulated is unclear. Here, we identify the Ca2+‐ and integrin‐binding protein 1 (CIB1) as a PDXP interactor by yeast two‐hybrid screening, and found a calmodulin (CaM)‐binding motif that overlaps with the PDXP‐CIB1 interaction site. Pulldown and crosslinking assays with purified proteins demonstrate that PDXP directly binds to CIB1 or CaM. CIB1 or CaM do not alter PDXP phosphatase activity. However, elevated Ca2+‐concentrations promote CaM binding and, thereby, diminished CIB1 binding to PDXP, as both interactors bind in a mutually exclusive way. Hence, the PDXP‐CIB1 complex may functionally differ from the PDXP‐Ca2+‐CaM complex.Funding Information
- Deutsche Forschungsgemeinschaft (SFB688, SFB728)
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