Fig. 8. The conserved N-terminal patch modulates lipid binding to the IDR.

a, b, c Chemical shift perturbation of ¹⁵N-labeled a IDR, b IDR^AAWAA, and c IDR^Patch titrated with short-chain PIP₂. Mutated regions are indicated in gray boxes, chemical shift changes are depicted by colored spheres, residues showing line broadening are highlighted by gray bars. d Average number of membrane contacts for each residue of the native IDR (dark gray), the IDR^AAWAA mutant (light gray) and the IDR^Patch mutant (mauve) on a lipid bilayer composed of POPC (69%), CHOL (20%), DOPS (10%), PIP₂ (1%) (Supplementary Table 4). The location of the N-terminal patch and the PIP₂-binding site (PBS) are highlighted by gray boxes. In the upper panel, contacts for all lipids, in lower panel, only contacts with PIP₂ are shown. Four replicate simulations per IDR sequence were carried out for 38 µs and contact averages were calculated from the last ~28 µs of each simulation. e ³¹P NMR spectra of diC₈-PIP₂ (light blue) with increasing amounts of IDR, IDR^ΔN97 or IDR^Patch. Chemical shift changes are indicated by arrows. f Chemical shift perturbations of P4 and P5 lipid headgroup resonances upon addition of IDR (gray), IDR^ΔN97 (blue), or IDR^Patch (mauve). Source data are provided as a Source Data file.