Fast antibody fragment motion: flexible linkers act as entropic spring
Abstract
A flexible linker region between three fragments allows antibodies to adjust their binding sites to an antigen or receptor. Using Neutron Spin Echo Spectroscopy we observed fragment motion on a timescale of 7 ns with motional amplitudes of about 1 nm relative to each other. The mechanistic complexity of the linker region can be described by a spring model with Brownian motion of the fragments in a harmonic potential. Displacements, timescale, friction and force constant of the underlying dynamics are accessed. The force constant exhibits a similar strength to an entropic spring, with friction of the fragment matching the unbound state. The observed fast motions are fluctuations in pre-existing equilibrium configurations. In conclusion, the Brownian motion of domains in a harmonic potential is the appropriate model to examine functional hinge motions dependent on the structural topology and highlights the role of internal forces and friction to function.
- Authors:
-
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source (SNS) and Julich Centre for Neutron Science (JCNS)
- Julich Research Centre, Garching (Germany). Julich Centre for Neutron Science (JCNS)
- Julich Research Centre and Inst. of Complex Systems, Julich (Germany). Julich Centre for Neutron Science (JCNS)
- Julich Research Centre and Inst. of Complex Systems, Julich (Germany). Julich Centre for Neutron Science (JCNS)
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1261399
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 6; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND TECHNOLOGY
Citation Formats
Stingaciu, Laura R., Ivanova, Oxana, Ohl, Michael, Biehl, Ralf, and Richter, Dieter. Fast antibody fragment motion: flexible linkers act as entropic spring. United States: N. p., 2016.
Web. doi:10.1038/srep22148.
Stingaciu, Laura R., Ivanova, Oxana, Ohl, Michael, Biehl, Ralf, & Richter, Dieter. Fast antibody fragment motion: flexible linkers act as entropic spring. United States. https://doi.org/10.1038/srep22148
Stingaciu, Laura R., Ivanova, Oxana, Ohl, Michael, Biehl, Ralf, and Richter, Dieter. Tue .
"Fast antibody fragment motion: flexible linkers act as entropic spring". United States. https://doi.org/10.1038/srep22148. https://www.osti.gov/servlets/purl/1261399.
@article{osti_1261399,
title = {Fast antibody fragment motion: flexible linkers act as entropic spring},
author = {Stingaciu, Laura R. and Ivanova, Oxana and Ohl, Michael and Biehl, Ralf and Richter, Dieter},
abstractNote = {A flexible linker region between three fragments allows antibodies to adjust their binding sites to an antigen or receptor. Using Neutron Spin Echo Spectroscopy we observed fragment motion on a timescale of 7 ns with motional amplitudes of about 1 nm relative to each other. The mechanistic complexity of the linker region can be described by a spring model with Brownian motion of the fragments in a harmonic potential. Displacements, timescale, friction and force constant of the underlying dynamics are accessed. The force constant exhibits a similar strength to an entropic spring, with friction of the fragment matching the unbound state. The observed fast motions are fluctuations in pre-existing equilibrium configurations. In conclusion, the Brownian motion of domains in a harmonic potential is the appropriate model to examine functional hinge motions dependent on the structural topology and highlights the role of internal forces and friction to function.},
doi = {10.1038/srep22148},
journal = {Scientific Reports},
number = ,
volume = 6,
place = {United States},
year = {Tue Mar 29 00:00:00 EDT 2016},
month = {Tue Mar 29 00:00:00 EDT 2016}
}
Web of Science
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