Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Poster Session II

25-POS Board 1 Disordered Proteins in the Eyes of a Molecular Chaperone Magdalena Wawrzyniuk 1 , Luca Ferrari 1 , Elif Karagöz 1,3 , Madelon M. Maurice 2 , Stefan G. Rüdiger 1 . 1 Utrecht University, Utrecht, Netherlands, 2 UMC, Utrecht, Netherlands, 3 UCSF, San Francisco, CA, USA. The Hsp90 family constitutes the most abundant cytoplasmic molecular chaperone system, which assists late stages of protein folding. Recently, we obtained a structural model of Hsp90 in complex with Tau, an intrinsically disordered protein [1]. This complex reveals how a disordered protein looks like in the eyes of a chaperone. Based on this paradigmatic interaction, we set out to extract general themes of Hsp90 substrate recognition, which aims to provide a general mechanistic view on why and when a molecular chaperone car recognize intrinsically disordered proteins. We developed an algorithm to identify stretches of similar properties in other disordered proteins. Based on this, here we present a bioinformatic tool for screening for potential Hsp90 binding sites among intrinsically disordered proteins. We further tested the predictions experimentally for a subset of substrates. As first target, we focused on the instrinsically disordered scaffold proteins of the destruction complex of the Wnt signaling cascade. Reference [1] Karagöz GE, Duarte AM, Akoury E, Ippel H, Biernat J, Morán Luengo T, Radli M, Didenko T, Nordhues BA, Veprintsev DB, Dickey CA, Mandelkow E, Zweckstetter M, Boelens R, Madl T, Rüdiger SGD. Hsp90-Tau complex reveals molecular basis for specificity in chaperone action (2014) Cell 156, 963-74.

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