6EIH

The crystal structure of 14-3-3 epsilon in complex with the phosphorylated NELFE peptide

Summary for 6EIH

• Entry DOI: 10.2210/pdb6eih/pdb
• Descriptor: 14-3-3 protein epsilon, SER-ILE-SEP-ARG (3 entities in total)
• Functional Keywords: 14-3-3, nelf, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 26913.56

Authors

Akutsu, M.,Wagner, S.A.,Beli, P. (deposition date: 2017-09-19, release date: 2018-02-14, Last modification date: 2019-10-16)

Primary citation

Borisova, M.E.,Voigt, A.,Tollenaere, M.A.X.,Sahu, S.K.,Juretschke, T.,Kreim, N.,Mailand, N.,Choudhary, C.,Bekker-Jensen, S.,Akutsu, M.,Wagner, S.A.,Beli, P.
p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage.
Nat Commun, 9:1017-1017, 2018

PubMed Abstract: Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV-light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here we employ quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway. We identify RNA-binding proteins as primary substrates and 14-3-3 as direct readers of p38-MK2-dependent phosphorylation induced by UV light. Mechanistically, we show that MK2 phosphorylates the RNA-binding subunit of the NELF complex NELFE on Serine 115. NELFE phosphorylation promotes the recruitment of 14-3-3 and rapid dissociation of the NELF complex from chromatin, which is accompanied by RNA polymerase II elongation.

PubMed: 29523821
DOI: 10.1038/s41467-018-03417-3

Experimental method

X-RAY DIFFRACTION (2.7 Å)