Fig. 1: Rationale of DisCO for partitioning target-specific Nbs that selectively bind to the SOS1•RAS complex only from those that only bind to the separate SOS1 or RAS protomers.
From: Allosteric nanobodies to study the interactions between SOS1 and RAS

a yeast cells displaying the ChILL immune library were incubated with SOS1 and RAS labeled with different fluorescent dyes. b FACS can then be used to sort yeast cells that display Nbs that bind to one of the protomers (Q1 or Q3) and others that are stained simultaneously by SOS1 and RAS (Q2). Supplementary Fig. 3 shows how this principle was put into practice to select competitive, connective and allosteric binders of the SOS1•RAS complex.