PhD student project 11
(Early Stage Researcher 11, ESR 11)
THE SUBSTRATE RECOGNITION SITE OF A CHAPERONE MACHINE
Supervision: Stefan Rüdiger
Early Stage Researcher: Martina Radli
The identification of the substrate-binding site of Hsp90 chaperones.
Based on the structural model of a Hsp90-substrate complex that we obtained recently, ESR11 will design mutants in Hsp90, predominantly in the binding interface. ESR11 will characterise those mutants (stability and conformational integrity), and test the mutants for substrate affinity (fluorescence and NMR, collaboration Boelens) and binding kinetics. ESR11 will compare the Tau binding site with those of other interactors, such as kinases and CFTR domains (collaboration Braakman), which will be produced in the human cell system (collaboration UPE). Structural models will be obtained by combining NMR with SAXS measurements (collaboration Madl). ESR11 will also analyse substrate-dependent ATPase stimulation and mutational effects. For comparison, ESR11 will also test whether the binding interface is conserved in the Hsp90 homologue Grp94 (collaboration Braakman and ESR2).
Boelens, Braakman; Madl (TU Munich); UPE
- G.E. Karagöz, A.M.S. Duarte, J. Ippel, C. Uetrecht, T. Sinnige, M. van Rosmalen , J. Hausmann, A.J.R. Heck, R. Boelens and S.G.D Rüdiger ‘The N-terminal domain of human Hsp90 triggers binding to the co-chaperone p23’, Proc Natl Acad Sci USA, 108, 580 (2011).
- D.P. Minde, Z. Anvarian, S.G.D. Rüdiger# and Maurice, MM# (2011) # joint corresponding authors. ‘Messing up disorder: How do missense mutations in the tumor suppressor protein APC lead to cancer?’ Mol Cancer 10, 101 (2011). Marked “highly accessed” by publisher.
- T. Didenko, R. Boelens and S.G.D. Rüdiger (2011). ‘3D DOSY–TROSY to determine the translational diffusion coefficient of large protein complexes.’ PEDS 24, 99-103.
Mapping substrate binding in the Hsp90 structure