Fast antibody fragment motion: flexible linkers act as entropic spring
- 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)
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.
- Research Organization:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Organization:
- USDOE
- Grant/Contract Number:
- AC05-00OR22725
- OSTI ID:
- 1261399
- Journal Information:
- Scientific Reports, Journal Name: Scientific Reports Vol. 6; ISSN 2045-2322
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Dual entropic and enthalpic processes in the lower critical solution temperature phase separation of poly(vinyl methyl ether) aqueous solutions
|
journal | January 2019 |
Dynamics of proteins in solution
|
journal | January 2019 |
Transition between protein-like and polymer-like dynamic behavior: Internal friction in unfolded apomyoglobin depends on denaturing conditions
|
journal | January 2020 |
Transition between protein-like and polymer-like dynamic behavior: Internal friction in unfolded apomyoglobin depends on denaturing conditions
|
text | January 2020 |
Similar Records
Radiolabeled antibody fragments
Impact of Linker Strain and Flexibility in the Design of a Fragment-Based Inhibitor
Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell lymphoma
Patent
·
Tue Jun 06 00:00:00 EDT 1989
·
OSTI ID:5468404
Impact of Linker Strain and Flexibility in the Design of a Fragment-Based Inhibitor
Journal Article
·
Wed Dec 31 23:00:00 EST 2008
· Nature Chemical Biology
·
OSTI ID:1020117
Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell lymphoma
Journal Article
·
Fri May 13 00:00:00 EDT 2016
· Biochemical and Biophysical Research Communications
·
OSTI ID:22596378