Figure 2.

Effect of the AP2M1 p.Arg170Trp Variant on the Thermodynamic Entropy of the AP-2 Complex

(A) Both the entire structure and a simplified cartoon model of the AP-2 complex are shown in the inactive closed state. The color-coding is a follows: AP-2α (blue), AP-2β (green), AP-2μ (magenta), AP-2 σ (orange), and the AP-2-bound cargo peptide P (yellow). The p.Arg170Trp variant is depicted as a red sphere. Further pathogenic variants in AP2S1 (AP-2σ) and rare population variants in AP2M1 (AP-2μ) variants are shown as golden spheres.

(B) Differences in entropy (entropic change; ΔG) between the wild-type (WT) AP-2 complex and the AP-2 complex containing the AP2M1 p.Arg170Trp variant are graphically depicted as ΔG for each residue across the entire AP-2 complex for the inactive closed state. The inlay shows an enlarged y axis to emphasize the differences in ΔG for each subunit.

(C) The structure of the AP-2 complex and a simplified cartoon model including the bound cargo peptide P (yellow) are shown in the active state, and the AP2S1 and AP2M1 variants are labelled.

(D) The difference in entropy between the WT AP-2 complex and the AP-2 complex containing the AP2M1 p.Arg170Trp variant for the active open state.