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Intrinsically disordered
proteins – biophysics and
protein-protein interactions
Intrinsically disordered proteins (IDPs) are an intriguing class of proteins extensively involved in regulation and protein-protein complexes of both high-affinity and transient nature. Defying the structure-function paradigm, such disordered regions are present in an estimated 30% of our proteome and the subject of intensive research by a wide range of methods. Notably, NMR presents tangible advantages for investigating this class of highly flexible and notoriously difficult to crystallize proteins. We have focused on our ‘pet’ IDP WASP-interacting protein (WIP), a 503-residue polypeptide that is mostly disordered, and particularly on specific regions, each 50-100 residues long, with defined biological roles. The WIP N-terminus contains two actin-binding modules, and its C-terminus forms (with WASP) a complex crucial in controlling actin polymerization and consequent cytoskeletal changes in T cells. Our efforts have uncovered novel binding epitopes in both terminal domains of WIP, and we are currently solving the structure of the WIP/WASP complex that explains the molecular basis of WIP chaperoning of WASP. We have also been involved in method development of NMR approaches suitable for studying IDPs with implementations for WIP and other proteins.



Novacek, J.; Haba, N.; Chill, J.H.; Zidek, L.; Sklenar, V.; 4D non-uniformly sampled HabCabCON/intra-HabCabNCO experiments for the sequential assignment and chemical shift analysis of intrinsically disordered proteins. J. Biomol. NMR 2012, 53(2), 139-148.

Bermel, W.; Bertini, I.; Chill, J.H.; Felli, I.C.; Haba, N.Y.; Kumar, M.V.; Pierattelli, R. 13C-direct detection amino acid selective NMR experiments to simplify the assignment of IDPs. ChemBioChem, 2012, 13(16), 2425-2432.

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.

Elazari-Shalom, H.; Shaked, H.; Esteban-Martin, S.; Salvatella, X.; Barda-Saad, M.; Chill, J.H. New insights into the role of the disordered WIP N-terminal domain revealed by NMR structural characterization. FEBS J., 2015, 282(4), 700-714.   

Rozentur-Shkop, E.; Goobes, G.; Chill, J.H. A J-modulated protonless NMR experiment characterizes the conformational ensemble of the intrinsically disordered protein WIP. J. Biomol NMR 2016, 66(4), 243-257.

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