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WAS is a rare-disease primary immunodeficiency caused by mutations in Wiskott-Aldrich syndrome protein (WASP). We have been studying the interaction between WASP and its molecular chaperon WIP using our structural NMR expertise. We are interested in what determines the affinity between WIP and WASP, what are the molecular principles underlying the loss of this affinity induced by WASP mutations, and how is the WIP/WASP interaction modulated by cellular signals such as phosphorylation? Our main findings are the discovery of a novel WIP binding epitope preceding the known WASP-binding region, and the determination of a working structural model of the complex providing a structural context for phosphorylation, degradation, effects of mutations, and more.


Haba, N.Y.; Gross, R.; Novacek, J.; Shaked, H.; Zidek, L,; Barda-Saad, M.; Chill, J.H.* NMR determines transient structure and dynamics in the disordered C-terminal domain of WASp interacting protein. Biophyiscal J. 2013, 105(2), 481-493. (*Corresponding author)

Fried, S.; Eliyaho, S.; Pauker, H.M.; Noy, E.; Reicher, B.; Chill, J.H. and Mira Barda-Saad. Triple color-FRET analysis reveals a dynamic conformational change within the actin regulating WIP:WASp complex. Science Signaling, 2014, 7(331):ra60. doi: 10.1126/scisignal.2005198.

Halle-Bikovski, A.; Fried, S.; Biber, G.; Rozentur-Shkop, E.; Joseph, N.; Shaked, H.; Barda-Saad, M.† Chill, J.H.† New structural insights into formation of the key actin regulating WIP-WASp complex determined by NMR and molecular imaging. ACS Chem. Biol. 2018, 13(1), 100-109.

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