4HKC

14-3-3-zeta in complex with S1011 phosphorylated integrin alpha-4 peptide

Summary for 4HKC

• Entry DOI: 10.2210/pdb4hkc/pdb
• Related: 2V7D
• Descriptor: 14-3-3 protein zeta/delta, alpha-4 integrin derived phosphorylated peptide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: 14-3-3, all-helical protein, regulatory, alpha-4 integrin tail, phosphorylation, signal transduction, signaling protein-peptide complex, signaling protein/peptide
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : P63104; Membrane; Single-pass type I membrane protein: P13612
• Total number of polymer chains: 2
• Total formula weight: 32078.63

Authors

Bonet, R.,Campbell, I.D. (deposition date: 2012-10-15, release date: 2013-06-26, Last modification date: 2024-10-30)

Primary citation

Bonet, R.,Vakonakis, I.,Campbell, I.D.
Characterization of 14-3-3-zeta Interactions with integrin tails
J.Mol.Biol., 425:3060-3072, 2013

PubMed Abstract: Integrins are a family of heterodimeric (α+β) adhesion receptors that play key roles in many cellular processes. Integrins are unusual in that their functions can be modulated from both outside and inside the cell. Inside-out signaling is mediated by binding adaptor proteins to the flexible cytoplasmic tails of the α- and β-integrin subunits. Talin is one well-known intracellular activator, but various other adaptors bind to integrin tails, including 14-3-3-ζ, a member of the 14-3-3 family of dimeric proteins that have a preference for binding phosphorylated sequence motifs. Phosphorylation of a threonine in the β2 integrin tail has been shown to modulate β2/14-3-3-ζ interactions, and recently, the α4 integrin tail was reported to bind to 14-3-3-ζ and associate with paxillin in a ternary complex that is regulated by serine phosphorylation. Here, we use a range of biophysical techniques to characterize interactions between 14-3-3-ζ and the cytoplasmic tails of α4, β1, β2 and β3 integrins. The X-ray structure of the 14-3-3-ζ/α4 complex indicates a canonical binding mode for the α4 phospho-peptide, but unexpected features are also observed: residues outside the consensus 14-3-3-ζ binding motif are shown to be essential for an efficient interaction; in contrast, a short β2 phospho-peptide is sufficient for high-affinity binding to 14-3-3-ζ. In addition, we report novel 14-3-3-ζ/integrin tail interactions that are independent of phosphorylation. Of the integrin tails studied, the strongest interaction with 14-3-3-ζ is observed for the β1A variant. In summary, new insights about 14-3-3-ζ/integrin tail interactions that have implications for the role of these molecular associations in cells are described.

PubMed: 23763993
DOI: 10.1016/j.jmb.2013.05.024

Experimental method

X-RAY DIFFRACTION (2.2 Å)