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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. 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.

SUBMITTER: Stingaciu LR

PROVIDER: S-EPMC4810366 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Stingaciu Laura R LR Ivanova Oxana O Ohl Michael M Biehl Ralf R Richter Dieter D

Scientific reports 20160329

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 dynamic ...[more]

PMID: 27020739

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