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

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Ca2+ functions as a molecular switch that controls the mutually exclusive complex formation of pyridoxal phosphatase with CIB1 or Calmodulin
FEBS Letters ( IF 3.0 ) Pub Date : 2020-05-19 , DOI: 10.1002/1873-3468.13795
Elisabeth Jeanclos _{1,

2,

3} , Gunnar Knobloch _{1,

2} , Axel Hoffmann _{1,

2,

4} , Oleg Fedorchenko ₄ , Andrea Odersky ₄ , Anna-Karina Lamprecht _{1,

2} , Hermann Schindelin ₂ , Antje Gohla _{1,

2,

4}

Affiliation

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 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.

中文翻译：

Ca2+ 作为分子开关，控制吡哆醛磷酸酶与 CIB1 或钙调蛋白相互排斥的复合物形成

5′-磷酸吡哆醛（PLP）是神经递质代谢的重要辅助因子。小鼠体内吡哆醛磷酸酶（PDXP）缺乏会增加大脑中 PLP 和 γ-氨基丁酸的水平，但 PDXP 的调节机制尚不清楚。在这里，我们通过酵母双杂交筛选将 Ca2+ 和整合素结合蛋白 1 (CIB1) 鉴定为 PDXP 相互作用蛋白，并发现与 PDXP-CIB1 相互作用位点重叠的钙调蛋白 (CaM) 结合基序。使用纯化蛋白进行的 Pulldown 和交联测定表明 PDXP 直接与 CIB1 或 CaM 结合。 CIB1 或 CaM 不会改变 PDXP 磷酸酶活性。然而，Ca2+ 浓度升高会促进 CaM 结合，从而减少 CIB1 与 PDXP 的结合，因为两种相互作用因子以相互排斥的方式结合。因此，PDXP-CIB1 复合物在功能上可能不同于 PDXP-Ca2+-CaM 复合物。

更新日期：2020-05-19

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