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A Unified View of “How Allostery Works”
Figure 6
The extended ATSM with two allosteric ligands.
(A) The model has ten species related by four equilibrium cycles with seven parameters. The first equilibrium cycle (orange) specified by the 
, 
, and 
is exactly the same as in the simplest ATSM (Figure 2A), giving 
the equilibrium constant between the two states, 
the binding affinity of ligand 
bound to inactive 
, and 
the allosteric intrinsic efficacy of ligand 
. The second equilibrium cycle 
(pale green) describes the second ligand binding similar to the first ligand binding, assigning 
and 
respectively as the binding affinity and the allosteric intrinsic efficacy of ligand 
. In the third equilibrium cycle 
(cyan), the sixth parameter 
administers the binding cooperativity between ligand 
and 
upon the formation of the ternary complex 
. Similarly, the seventh parameter 
governs the activation cooperativity between ligand 
and 
through the formation of 
in the fourth equilibrium cycle 
(red). (B) The complete equilibrium cycles of the extended ATSM. The four essential equilibrium cycles of the extended ATSM in (A) are combined into a cubic shape of a complete cycle. To guide the visualization, the two corners of the complete cycle are highlighted by colored equilibrium arrows for species 
and 
and colored parameters for referencing back to the individual essential equilibrium cycle. (C) The structural view of allostery with two allosteric site and two (independent) functional sites. The drawing is based on two assumptions. First, the populations of the two functional sites are regulated independently by two distinct allosteric sites. Second, the two functional conformations coexist. The allosteric coupling set (
, 
, and 
) for functional site 1 and a duplicated set of independent allosteric efficacies (
, 
, and 
) for functional site 2 are similar to the description in Figure 6B. These two sets of coupling are linked by a shared binding cooperativity γ, coupling the two allosteric sites.
doi: https://doi.org/10.1371/journal.pcbi.1003394.g006