Phosphorylation-dependent conformational change in the Keratin 19 head domain: Implications for filament assembly and binding to GSK3β and 14-3-3

Phosphomimetic S35E in the Keratin 19 (K19) head domain is linked to phosphorylation-dependent conformational changes that alter binding to GSK3β and K8/K19 filaments.

• Why it matters: Binding-site details and molecular mechanisms for K19 interactions with signaling partners are unclear, and atomic-resolution structures for K19 head-domain IDRs are lacking.
• What they did: Using NMR spectroscopy, solution structures were obtained for K19 head domain peptides, and phosphomimetic peptides (including S35E) were modeled to test conformational effects on partner binding.
• The result: NMR spectral changes showed S35E affects association with K8/K19 filaments and GSK3β, while no significant binding changes were observed with 14-3-3ζ and 14-3-3σ; in 293T cells it altered filament organization and reduced K19–GSK3β proximity, with no significant change for K19–14-3-3σ.

AI summary of the abstract · may contain errors · not medical advice · read the paper.