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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