Fig. 2
From: Structural determinants and functional consequences of protein affinity for membrane rafts
TMD surface area determines raft partitioning. a For 56 TMD constructs, computed side chain surface area correlates strongly with raft affinity (r = 0.74, p < 0.001), with TMDs with smaller areas preferentially partitioning to the raft phase. b Schematic model for accessible surface area (ASA)-dependent raft affinity based on differential interfacial tension (ΔγTMD,Lo-Ld) between a TMD and the membrane matrix in raft versus non-raft phases. c Apparent raft affinity ΔGraft,app for 12 constructs whose TMDs are comprised solely of Ala and Leu residues shows a clear dependence on TMD side chain surface area. The dotted line shows the model fit, which yields a prediction for ΔγTMD,Lo-Ld of 1.1 pN/nm (r = 0.93, p<0.001). Average±SD for > 10 vesicles/condition representative of 3–5 independent trials. Sequences and partitioning values for all variants are given in Supplementary Table 2. d Endpoint snapshots of CG MD simulations of model TMDs (yellow) with small (all-Ala) and large (all-Phe) surface areas in a phase separated membrane composed of 50% DPPC (blue), 30% DLiPC (green), and 20% cholesterol (white). e Quantification of contacts between TMDs and lipids reveals that all-Ala interacts more avidly with Lo lipids (DPPC+Chol) than Ld lipids (DLiPC). f Umbrella sampling calculation of relative free energy (PMF) difference resulting from translating a TMD from the center of the Lo domain (x = 0 nm) to the Ld (x = 6 nm). all-Ala has much higher relative Lo affinity than all-Phe
