Ca2+ functions as a molecular switch that controls the mutually exclusive complex formation of pyridoxal phosphatase with CIB1 or calmodulin

Jeanclos, Elisabeth; Knobloch, Gunnar; Hoffmann, Axel; Fedorchenko, Oleg; Odersky, Andrea; Lamprecht, Anna-Karina; Schindelin, Hermann und Gohla, Antje (2020): Ca2+ functions as a molecular switch that controls the mutually exclusive complex formation of pyridoxal phosphatase with CIB1 or calmodulin. In: FEBS Letters, Bd. 594, Nr. 13: S. 2099-2115

Abstract

Pyridoxal 5 '-phosphate (PLP) is an essential cofactor for neurotransmitter metabolism. Pyridoxal phosphatase (PDXP) deficiency in mice increases PLP and gamma-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 find 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 does not alter PDXP phosphatase activity. However, elevated Ca2+ concentrations promote CaM binding and, thereby, diminish 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0014-5793
• Sprache: Englisch