Memory of Periodic Thermal Stimulation in an Immune Complex

Proteins search their conformational space in order to attain the native fold and bind productively to relevant biological partners. Most proteins must be able to alternate between at least one active conformational state back to an inactive conformer, especially for macromolecules that perform work and need to optimize energy usage. This property may be invoked by a physical stimulus (eg. temperature) or by a chemical ligand, and may occur through mapping of the protein external environment onto a subset of protein conformers. We have stimulated with temperature cycles two partners of an immune complex before and after assembly. We have revealed with calorimetry that properties of the external stimulus are also found in the characteristics of the immune complex (i. e. periodic variations in the binding affinity). These results are important for delineating the bases of molecular memory ex vivo and may serve in the optimization of protein based sensors. Stimulation in vitro with temperature waveforms of two proteins partners, prior to or after complex formation revealed corresponding periodic changes in their thermodynamic and kinetic binding parameters, after removal of the external stimulus. The capacity to retain and revisit specific protein conformational states, in the absence of the initial stimulus, is a feature of molecular memory.