Utility of FRET in studies of membrane protein oligomerization: the concept of the effective dissociation constant

Biophys J. 2023 Sep 21:S0006-3495(23)00588-X. doi: 10.1016/j.bpj.2023.09.011. Online ahead of print.ABSTRACTThe activity of many membrane receptors is controlled through their lateral association into dimers or higher order oligomers. While Förster resonance energy transfer (FRET) measurements have been used extensively to characterize the stability of receptor dimers, the utility of FRET in studies of larger oligomers has been limited. Here we introduce an effective equilibrium dissociation constant that can be extracted from FRET measurements for EphA2, a receptor tyrosine kinase (RTK) known to form active oligomers of heterogeneous distributions in response to its ligand ephrinA1-Fc. The newly introduced effective equilibrium dissociation constant has a well-defined physical meaning and biological significance. It denotes the receptor concentration for which half of the receptors are monomeric and inactive, and the other half are associated into oligomers and are active, irrespective of the exact oligomer size. This work introduces a new dimension to the utility of FRET in studies of membrane receptor association and signaling in the plasma membrane.PMID:37735871 | DOI:10.1016/j.bpj.2023.09.011

Source: Biophysical Journal - September 22, 2023 Category: Physics Authors: Daniel McKenzie Daniel Wirth Taras V Pogorelov Kalina Hristova Source Type: research