title: 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.
authors.affiliation: Jülich Centre for Neutron Science JCNS, Forschungszentrum Jülich GmbH, outstation at SNS, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Stingaciu
authors.affiliation: Jülich Centre for Neutron Science JCNS, Forschungszentrum Jülich GmbH, outstation at MLZ, 85747 Garching, Germany.
authors.forename: Oxana
authors.initials: O
authors.lastname: Ivanova
authors.affiliation: Jülich Centre for Neutron Science JCNS, Forschungszentrum Jülich GmbH, outstation at SNS, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ohl
authors.affiliation: Jülich Centre for Neutron Science JCNS (JCNS-1) &Institute of Complex Systems (ICS-1), Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Biehl
authors.affiliation: Jülich Centre for Neutron Science JCNS (JCNS-1) &Institute of Complex Systems (ICS-1), Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Richter
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D019277:Entropy; D017276:Friction; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry* / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009038:Motion; D033363:Neutron Diffraction; D011485:Protein Binding; D000072417:Protein Domains; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G