PuSH - Publication Server of Helmholtz Zentrum München

Lopez, A. ; Elimelech, A.R.* ; Klimm, K.* ; Sattler, M.

The charged linker modulates the conformations and molecular interactions of Hsp90.

ChemBioChem, DOI: 10.1002/cbic.202000699 (2021)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The molecular chaperone Hsp90 supports the functional activity of specific substrate proteins (clients). For client processing, the Hsp90 dimer undergoes a series of ATP-driven conformational rearrangements. Flexible linkers connecting the three domains of Hsp90 are crucial to enable dynamic arrangements. The long charged linker connecting the N-terminal (NTD) and middle (MD) domains exhibits additional functions in vitro and in vivo. The structural basis for these functions remains unclear. Here, we characterize the conformation and dynamics of the linker and NTD−MD domain interactions by NMR spectroscopy. Our results reveal two regions in the linker that are dynamic and exhibit secondary structure conformation. We show that these regions mediate transient interactions with strand β8 of the NTD. As a consequence, this strand detaches and exposes a hydrophobic surface patch, which enables binding to the p53 client. We propose that the charged linker plays an important regulatory role by coupling the Hsp90 NTD−MD arrangement with the accessibility of a client binding site on the NTD.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Charged Linkers ; Client Interactions ; Dynamics ; Hsp90 ; Nmr Spectroscopy; N-terminal Domain; Heat-shock-protein; Structural-analysis; Nmr; Cycle; Reveals; Binding; Phosphorylation; Identification; Dynamics
ISSN (print) / ISBN 1439-4227
e-ISSN 1439-7633
Journal ChemBioChem
Publisher Wiley
Publishing Place Postfach 101161, 69451 Weinheim, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
Grants German Research Foundation