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Title: Fast antibody fragment motion: flexible linkers act as entropic spring

Journal Article · · Scientific Reports
DOI:https://doi.org/10.1038/srep22148· OSTI ID:1261399
 [1];  [2];  [1];  [3];  [4]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source (SNS) and Julich Centre for Neutron Science (JCNS)
  2. Julich Research Centre, Garching (Germany). Julich Centre for Neutron Science (JCNS)
  3. Julich Research Centre and Inst. of Complex Systems, Julich (Germany). Julich Centre for Neutron Science (JCNS)
  4. 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 Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
1261399
Journal Information:
Scientific Reports, Vol. 6; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 23 works
Citation information provided by
Web of Science

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Cited By (4)

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

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