Abstract
When characterizing biomolecular interactions, avidity, is an umbrella term used to describe the accumulated strength of multiple specific and unspecific interactions between two or more interaction partners. In contrast to the affinity, which is often sufficient to describe monovalent interactions in solution and where the binding strength can be accurately determined by considering only the relationship between the microscopic association and dissociation rates, the avidity is a phenomenological macroscopic parameter linked to several microscopic events. Avidity also covers potential effects of reduced dimensionality and/or hindered diffusion observed at or near surfaces e.g., at the cell membrane. Avidity is often used to describe the discrepancy or the “extra on top” when cellular interactions display binding that are several orders of magnitude stronger than those estimated in vitro. Here we review the principles and theoretical frameworks governing avidity in biological systems and the methods for predicting and simulating avidity. While the avidity and effects thereof are well-understood for extracellular biomolecular interactions, we present here examples of, and discuss how, avidity and the underlying kinetics influences intracellular signaling processes.
Highlights
Cell function relies on meticulously timed dynamic networks of biomolecular interactions taking place in changeable cellular compartments with great variability in size, shape, pH, solute concentration, and molecular crowding
The association and dissociation rates depend on the type of interaction and external physical properties (Calef and Deutch, 1983) and may span several orders of magnitude. kon ranges from 109 M−1s−1 for the fastest diffusion limited reactions that are enhanced by electrostatic interactions to 104 M−1s−1 for slow reactions that often are governed by large conformational changes (Schreiber and Fersht, 1996; Dogan et al, 2014). koff depends on how fast the intermolecular interactions that stabilize the complex are broken and typically ranges between 104 and 10−4 s−1
We found that changing the intrinsic affinity from 1 to 10 μM, resulted in a complete switch between a multivalent and monovalent interaction mode at physiological protein concentrations, and that only one of these modes resulted in recycling of ligand receptors
Summary
Cell function relies on meticulously timed dynamic networks of biomolecular interactions taking place in changeable cellular compartments with great variability in size, shape, pH, solute concentration, and molecular crowding. All these parameters affect diffusion and reaction rates. The microscopic rate constants for the above reaction are called the association rate constant, kon, and dissociation rate constant, koff. The relation between these parameters and the equilibrium concentrations of species A, a and Aa are given by: Kd =
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