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Antibodies in Solution: a LINXS - NIST Webinar Series with Ralf Biehl - IPDD theme

When: 7 February, 2024, 15:30 - 16:30 CET

Speaker: Ralf Biehl, Jülich Centre for Neutron Science (JCNS), Germany.

Title: Domain Motions: Protein Dynamics seen by Neutron Spinecho Spectroscopy

Abstract

The biological function of proteins is often related to configurational changes and large-scale domain motions, which are induced or suppressed by the binding of a substrate or due to cosolvents. Domain motions can be related to soft hinges, flexible linker regions or -as in the case of intrinsically disordered proteins- be native to proteins without secondary or tertiary structure. These large-scale domain motions in solution cannot be observed by X-ray crystallography or NMR spectroscopy. Small angle scattering (SAS) by X-rays or neutrons in combination with neutron spin echo spectroscopy (NSE) in solution can be used to observe configurational changes and equilibrium dynamics between functional domains on 1-300 nanosecond timescale.

I will present examples for different types of motions related to the structure of proteins and bioconjugates. Thermal unfolded Ribonuclease A shows polymer like dynamics despite the 4 disulfide bonds restricting the degrees of freedom. Prior to full unfolding the protein unfolding dynamics is observed. Polyelectrolytes have structural and dynamical similarities with IDP. The domain protein Phosphoglycerate kinase shows a hinge motion between the main domains related to function. PEGylation seems not to influence this domain motion but adds additional internal dynamics in the protein-polymer complex. Antibodies present a strong dynamics due to the short linkers connecting the Fc with the Fab domains. The observed dynamics is related to internal forces, solvent friction and the role of charge screening.

Bio

 Ralf Biehl received his PhD in Physics from the University Mainz, Germany in 2002 doing optical shear rheology on colloids. After his postdoctoral time as instrument scientist at the NSE instrument in Jülich he became staff scientist at JCNS in Jülich in 2008. From 2014-2019 he was member, later chair, of the subcommittee Biology at ILL. His general interest is to identify functional domain motion and characterize timescale and amplitudes by combining neutron scattering methods like NSE with other complementary biophysical methods.

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