Fig. 2. Conformational changes in p110α core compared to full-length p110α- p85α, and comparison to changes upon pY/Ras membrane recruitment.

A Peptides in p110α that showed significant differences in HDX (>0.4 Da and 5% difference, with a two-tailed t-test p < 0.01) between the catalytic core and the full-length complex are mapped on the structure of p110α-p85α complex (PDB: 4OVU [https://www.rcsb.org/structure/4ovu].) according to the legend. The regions of the ABD (pink) and p85 (green) that are missing in the p110α core are shown as a surface. Cartoon models representing the differences between states are shown next to the structures. A more extensive set of peptides are shown in Supplementary Fig.4. B Peptides in p110α that showed significant differences in both p110α and p85α between free (with pY) and membrane-bound (pY, membrane Ras) (data adapted from Siempelkamp et al.¹²) are mapped onto the structure of p110α-p85α (PDB: 4OVU) according to the legend. Data are presented as the mean, with error bars representing SD (n = 3). C The sum of the number of deuteron difference for all peptides analysed over the entire deuterium exchange time course for p110α core compared to full-length p110α- p85α. Peptides coloured in red are those that had a significant change (>0.4 Da and 5% difference at any timepoint, with a two-tailed t-test p < 0.01). Each point represents a single peptide, and error bars are shown as the sum of S.D. across all time points (n = 3 for each time point). D Selected p110α peptide in the ABD-RBD linker that showed increases in exchange in p110α core compared to full-length p110α-p85α (left), and upon membrane binding of full-length PI3K (right, data adapted from Siempelkamp et al.¹²). (Mean is shown, with error bars representing S.D., n = 3)., with smaller than the size of the point. A more extensive set of peptides comparing the full-length p110α-p85α with p110α core are shown in Supplementary Fig. 4, with the full list of all peptides and their deuterium incorporation in the source data file.