6TWZ

14-3-3 sigma complexed with a phosphorylated 16E6 peptide

This is a non-PDB format compatible entry.

Summary for 6TWZ

• Entry DOI: 10.2210/pdb6twz/pdb
• Descriptor: 14-3-3 protein sigma, phosphorylated 16E6 peptide, D(-)-TARTARIC ACID, ... (4 entities in total)
• Functional Keywords: phosphorylation, motif, 14-3-3 protein, peptide binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 111178.19

Authors

Gogl, G.,Cousido-Siah, A.,Sluchanko, N.N.,Trave, G. (deposition date: 2020-01-13, release date: 2020-05-06, Last modification date: 2024-10-09)

Primary citation

Gogl, G.,Jane, P.,Caillet-Saguy, C.,Kostmann, C.,Bich, G.,Cousido-Siah, A.,Nyitray, L.,Vincentelli, R.,Wolff, N.,Nomine, Y.,Sluchanko, N.N.,Trave, G.
Dual Specificity PDZ- and 14-3-3-Binding Motifs: A Structural and Interactomics Study.
Structure, 28:747-759.e3, 2020

PubMed Abstract: Protein-protein interaction motifs are often alterable by post-translational modifications. For example, 19% of predicted human PDZ domain-binding motifs (PBMs) have been experimentally proven to be phosphorylated, and up to 82% are theoretically phosphorylatable. Phosphorylation of PBMs may drastically rewire their interactomes, by altering their affinities for PDZ domains and 14-3-3 proteins. The effect of phosphorylation is often analyzed by performing "phosphomimetic" mutations. Here, we focused on the PBMs of HPV16-E6 viral oncoprotein and human RSK1 kinase. We measured the binding affinities of native, phosphorylated, and phosphomimetic variants of both PBMs toward the 266 human PDZ domains. We co-crystallized all the motif variants with a selected PDZ domain to characterize the structural consequence of the different modifications. Finally, we elucidated the structural basis of PBM capture by 14-3-3 proteins. This study provides novel atomic and interactomic insights into phosphorylatable dual specificity motifs and the differential effects of phosphorylation and phosphomimetic approaches.

PubMed: 32294469
DOI: 10.1016/j.str.2020.03.010

Experimental method

X-RAY DIFFRACTION (2.8 Å)