Advances in native mass spectrometry and single-molecule techniques have made it possible in recent years to determine the values of successive ligand binding constants for large multi-subunit proteins. Given these values, it is possible to distinguish between different allosteric mechanisms and, thus, obtain insights into how various bio-molecular machines work. Here, we describe for ring-shaped homo-oligomers, in particular, how the relationship between the values of successive ligand binding constants is diagnostic for concerted, sequential and probabilistic allosteric mechanisms.
This article is part of a discussion meeting issue ‘Allostery and molecular machines’.
Multiplexed Screening of Thousands of Natural Products for Protein–Ligand Binding in Native Mass Spectrometry
