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Ca\(^{2+}\) functions as a molecular switch that controls the mutually exclusive complex formation of pyridoxal phosphatase with CIB1 or calmodulin

Please always quote using this URN: urn:nbn:de:bvb:20-opus-217963
  • 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 Ca\(^{2+}\)‐ 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 CIB1Pyridoxal 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 Ca\(^{2+}\)‐ 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 Ca\(^{2+}\) 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‐Ca\(^{2+}\)‐CaM complex.show moreshow less

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Metadaten
Author: Elisabeth Jeanclos, Gunnar Knobloch, Axel Hoffmann, Oleg Fedorchenko, Andrea Odersky, Anna‐Karina Lamprecht, Hermann Schindelin, Antje Gohla
URN:urn:nbn:de:bvb:20-opus-217963
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Pharmakologie und Toxikologie
Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:English
Parent Title (English):FEBS Letters
Year of Completion:2020
Volume:594
Issue:13
First Page:2099
Last Page:2115
Source:FEBS Letters 2020, 594(13):2099-2115. DOI: 10.1002/1873-3468.13795
DOI:https://doi.org/10.1002/1873-3468.13795
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:CIB1; calmodulin; chronophin; haloacid dehalogenase; pyridoxal phosphatase; vitamin B6
Release Date:2021/08/18
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International