Flexibility of the PDZ-binding motif in the micelle-bound form of Jagged-1 cytoplasmic tail

Citations of this article
Mendeley users who have this article in their library.


Human Jagged-1, one of the ligands of Notch receptors, is a transmembrane protein composed of a large extracellular region and a 125-residue cytoplasmic tail which bears a C-terminal PDZ recognition motif. To investigate the interaction between Jagged-1 cytoplasmic tail and the inner leaflet of the plasma membrane we determined, by solution NMR, the secondary structure and dynamics of the recombinant protein corresponding to the intracellular region of Jagged-1, J1-tmic, bound to negatively charged lysophospholipid micelles. NMR showed that the PDZ binding motif is preceded by four α-helical segments and that, despite the extensive interaction between J1-tmic and the micelle, the PDZ binding motif remains highly flexible. Binding of J1-tmic to negatively charged, but not to zwitterionic vesicles, was confirmed by surface plasmon resonance. To study the PDZ binding region in more detail, we prepared a peptide corresponding to the last 24 residues of Jagged-1, J1C24, and different phosphorylated variants of it. J1C24 displays a marked helical propensity and undergoes a coil-helix transition in the presence of negatively charged, but not zwitterionic, lysophospholipid micelles. Phosphorylation at different positions drastically decreases the helical propensity of the peptides and abolishes the coil-helix transition triggered by lysophospholipid micelles. We propose that phosphorylation of residues upstream of the PDZ binding motif may shift the equilibrium from an ordered, membrane-bound, interfacial form of Jagged-1 C-terminal region to a more disordered form with an increased accessibility of the PDZ recognition motif, thus playing an indirect role in the interaction between Jagged-1 and the PDZ-containing target protein. © 2012 Elsevier B.V. All rights reserved.




Popovic, M., Zlatev, V., Hodnik, V., Anderluh, G., Felli, I. C., Pongor, S., & Pintar, A. (2012). Flexibility of the PDZ-binding motif in the micelle-bound form of Jagged-1 cytoplasmic tail. Biochimica et Biophysica Acta - Biomembranes, 1818(7), 1706–1716. https://doi.org/10.1016/j.bbamem.2012.03.012

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free