Sluchanko, Nikolai N, Beelen, Steven, Kulikova, Alexandra A et al. (4 more authors) (2017) Structural basis for the interaction of a human small heat shock protein with the 14-3-3 universal signaling regulator. Structure. 305–316. ISSN 1878-4186
Abstract
By interacting with hundreds of protein partners, 14-3-3 proteins coordinate vital cellular processes. Phosphorylation of the small heat shock protein, HSPB6, within its intrinsically disordered N-terminal domain activates its interaction with 14-3-3, ultimately triggering smooth muscle relaxation. After analyzing the binding of an HSPB6-derived phosphopeptide to 14-3-3 using isothermal calorimetry and X-ray crystallography, we have determined the crystal structure of the complete assembly consisting of the 14-3-3 dimer and full-length HSPB6 dimer and further characterized this complex in solution using fluorescence spectroscopy, small-angle X-ray scattering, and limited proteolysis. We show that selected intrinsically disordered regions of HSPB6 are transformed into well-defined conformations upon the interaction, whereby an unexpectedly asymmetric structure is formed. This structure provides the first atomic resolution snapshot of a human small HSP in functional state, explains how 14-3-3 proteins sequester their regulatory partners, and can inform the design of small-molecule interaction modifiers to be used as myorelaxants.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Elsevier B.V. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 02 May 2017 08:20 |
Last Modified: | 16 Oct 2024 13:31 |
Published Version: | https://doi.org/10.1016/j.str.2016.12.005 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.str.2016.12.005 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115875 |
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