Fig. 7

Proposed model of pH-dependent LLPS of HBP-derived peptides. At pH 3–4 His residues are protonated, and the peptides form soluble oligomeric units due to electrostatic repulsion between positively charged His side chains. At pH 4–6 gradual deprotonation of His residues occurs, repulsive forces are weaker but still strong enough to keep the peptide oligomers soluble. At pH 6–7 transient interactions take place between His and Tyr residues located within GHGxY repeats (marked in green) leading to specific peptide-peptide interactions that act as nuclei for LLPS. Further increase of pH above 7 leads to Tyr–Tyr intermolecular stacking and intra-molecular interaction of hydrophobic residues that all together trigger LLPS and the formation of microdroplets. If the central domain of the peptide is enriched with the hydrophobic motif GAGFA (marked in red) or with the His-rich motif GHGLH (marked in blue), LLPS is driven by the same sequence of molecular events but eventually leads to the formation of either a hydrogel or coacervate micro-droplets, respectively.