Controllable activation of nanoscale dynamics in a disordered protein alters binding kinetics
Abstract
The phosphorylation of specific residues in a flexible disordered activation loop yields precise control of signal transduction. One paradigm is the phosphorylation of S339/S340 in the intrinsically disordered tail of the multi-domain scaffolding protein NHERF1, which affects the intracellular localization and trafficking of NHERF1 assembled signaling complexes. Using neutron spin echo spectroscopy (NSE), we show salt-concentration-dependent excitation of nanoscale motion at the tip of the C-terminal tail in the phosphomimic S339D/S340D mutant. The “tip of the whip” that is unleashed is near the S339/S340 phosphorylation site and flanks the hydrophobic Ezrin-binding motif. The kinetic association rate constant of the binding of the S339D/S340D mutant to the FERM domain of Ezrin is sensitive to buffer salt concentration, correlating with the excited nanoscale dynamics. The results suggest that electrostatics modulates the activation of nanoscale dynamics of an intrinsically disordered protein, controlling the binding kinetics of signaling partners. Furthermore NSE can pinpoint the nanoscale dynamics changes in a highly specific manner.
- Authors:
-
[3];
[1]
- City College of New York, CUNY, New York, NY (United States)
- SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source (SNS)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1349622
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Molecular Biology
- Additional Journal Information:
- Journal Volume: 429; Journal Issue: 7; Journal ID: ISSN 0022-2836
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; nanoscale protein motion; disordered protein; protein binding kinetics; neutron spin echo spectroscopy; protein dynamics
Citation Formats
Callaway, David J. E., Matsui, Tsutomu, Weiss, Thomas, Stingaciu, Laura R., Stanley, Christopher B., Heller, William T., and Bu, Zimei. Controllable activation of nanoscale dynamics in a disordered protein alters binding kinetics. United States: N. p., 2017.
Web. doi:10.1016/j.jmb.2017.03.003.
Callaway, David J. E., Matsui, Tsutomu, Weiss, Thomas, Stingaciu, Laura R., Stanley, Christopher B., Heller, William T., & Bu, Zimei. Controllable activation of nanoscale dynamics in a disordered protein alters binding kinetics. United States. https://doi.org/10.1016/j.jmb.2017.03.003
Callaway, David J. E., Matsui, Tsutomu, Weiss, Thomas, Stingaciu, Laura R., Stanley, Christopher B., Heller, William T., and Bu, Zimei. Wed .
"Controllable activation of nanoscale dynamics in a disordered protein alters binding kinetics". United States. https://doi.org/10.1016/j.jmb.2017.03.003. https://www.osti.gov/servlets/purl/1349622.
@article{osti_1349622,
title = {Controllable activation of nanoscale dynamics in a disordered protein alters binding kinetics},
author = {Callaway, David J. E. and Matsui, Tsutomu and Weiss, Thomas and Stingaciu, Laura R. and Stanley, Christopher B. and Heller, William T. and Bu, Zimei},
abstractNote = {The phosphorylation of specific residues in a flexible disordered activation loop yields precise control of signal transduction. One paradigm is the phosphorylation of S339/S340 in the intrinsically disordered tail of the multi-domain scaffolding protein NHERF1, which affects the intracellular localization and trafficking of NHERF1 assembled signaling complexes. Using neutron spin echo spectroscopy (NSE), we show salt-concentration-dependent excitation of nanoscale motion at the tip of the C-terminal tail in the phosphomimic S339D/S340D mutant. The “tip of the whip” that is unleashed is near the S339/S340 phosphorylation site and flanks the hydrophobic Ezrin-binding motif. The kinetic association rate constant of the binding of the S339D/S340D mutant to the FERM domain of Ezrin is sensitive to buffer salt concentration, correlating with the excited nanoscale dynamics. The results suggest that electrostatics modulates the activation of nanoscale dynamics of an intrinsically disordered protein, controlling the binding kinetics of signaling partners. Furthermore NSE can pinpoint the nanoscale dynamics changes in a highly specific manner.},
doi = {10.1016/j.jmb.2017.03.003},
journal = {Journal of Molecular Biology},
number = 7,
volume = 429,
place = {United States},
year = {Wed Mar 08 00:00:00 EST 2017},
month = {Wed Mar 08 00:00:00 EST 2017}
}
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