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由二聚体和单体14-3-3ζ识别的微管相关蛋白2c上多个结合位点的表征

Characterization of multiple binding sites on microtubule associated protein 2c recognized by dimeric and monomeric 14-3-3ζ.

作者信息

Jansen Séverine, Narasimhan Subhash, Cabre Fernandez Paula, Iľkovičová Lucia, Kozeleková Aneta, Králová Kateřina, Hritz Jozef, Žídek Lukáš

机构信息

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.

National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic.

出版信息

FEBS J. 2025 Apr;292(8):1991-2016. doi: 10.1111/febs.17405. Epub 2025 Jan 29.

DOI:10.1111/febs.17405
PMID:39877981
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12001206/
Abstract

Microtubule associated protein 2 (MAP2) interacts with the regulatory protein 14-3-3ζ in a cAMP-dependent protein kinase (PKA) phosphorylation dependent manner. Using selective phosphorylation, calorimetry, nuclear magnetic resonance, chemical crosslinking, and X-ray crystallography, we characterized interactions of 14-3-3ζ with various binding regions of MAP2c. Although PKA phosphorylation increases the affinity of MAP2c for 14-3-3ζ in the proline rich region and C-terminal domain, unphosphorylated MAP2c also binds the dimeric 14-3-3ζ via its microtubule binding domain and variable central domain. Monomerization of 14-3-3ζ leads to the loss of affinity for the unphosphorylated residues. In neuroblastoma cell extract, MAP2c is heavily phosphorylated by PKA and the proline kinase ERK2. Although 14-3-3ζ dimer or monomer do not interact with the residues phosphorylated by ERK2, ERK2 phosphorylation of MAP2c in the C-terminal domain reduces the binding of MAP2c to both oligomeric variants of 14-3-3ζ.

摘要

微管相关蛋白2（MAP2）以一种依赖于环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）磷酸化的方式与调节蛋白14-3-3ζ相互作用。我们运用选择性磷酸化、量热法、核磁共振、化学交联以及X射线晶体学等方法，对14-3-3ζ与MAP2c不同结合区域的相互作用进行了表征。尽管PKA磷酸化增加了富含脯氨酸区域和C末端结构域中MAP2c对14-3-3ζ的亲和力，但未磷酸化的MAP2c也可通过其微管结合结构域和可变中央结构域与二聚体14-3-3ζ结合。14-3-3ζ的单体化导致其对未磷酸化残基的亲和力丧失。在神经母细胞瘤细胞提取物中，MAP2c被PKA和脯氨酸激酶ERK2大量磷酸化。尽管14-3-3ζ二聚体或单体不与ERK2磷酸化的残基相互作用，但MAP2c在C末端结构域的ERK2磷酸化会降低MAP2c与14-3-3ζ两种寡聚变体的结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/7e5b36a2b10c/FEBS-292-1991-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/7e5b36a2b10c/FEBS-292-1991-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/eaaa4dc7e73b/FEBS-292-1991-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/badf97e49237/FEBS-292-1991-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/4850f52b17ed/FEBS-292-1991-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/7514a61cbdee/FEBS-292-1991-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/40462496f4e4/FEBS-292-1991-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/319477df1cde/FEBS-292-1991-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/57218ef92251/FEBS-292-1991-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/55e4e9ee322e/FEBS-292-1991-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/605049ec32e2/FEBS-292-1991-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/674c27a480bc/FEBS-292-1991-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca97/12001206/7e5b36a2b10c/FEBS-292-1991-g006.jpg

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