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Dimeric 14-3-3 zeta in complex with MAP2c peptide containing pS435
Structural highlights
Function1433Z_HUMAN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.[1] [2] [3] [4] [5] Publication Abstract from PubMedMicrotubule associated protein 2 (MAP2) interacts with the regulatory protein 14-3-3zeta 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 14-3-3zeta with various binding regions of MAP2c. Although PKA phosphorylation increases the affinity of MAP2c for 14-3-3zeta in the proline rich region and C-terminal domain, unphosphorylated MAP2c also binds the dimeric 14-3-3zeta via its microtubule binding domain and variable central domain. Monomerization of 14-3-3zeta 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 14-3-3zeta 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 14-3-3zeta. Characterization of multiple binding sites on microtubule associated protein 2c recognized by dimeric and monomeric 14-3-3zeta.,Jansen S, Narasimhan S, Cabre Fernandez P, Ilkovicova L, Kozelekova A, Kralova K, Hritz J, Zidek L FEBS J. 2025 Jan 29. doi: 10.1111/febs.17405. PMID:39877981[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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